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ObjectiveTo observe the intervention effect of Dahuang Xiezhuo prescription （DHXZ） on inflammation and suppressor of cytokine signaling 3 （SOCS3）/Toll-like receptor 4 （TLR4） pathway in rats with chronic renal failure （CRF）， and to explore its molecular mechanism in alleviating renal inflammatory response. MethodThe 90 male SD rats， 15 were randomly selected as sham group， and the remaining 75 were used as modeling group to replicate CRF rat model by 5/6 nephrectomy. After successful modeling， the rats were randomly divided into model group， DHXZ low-， medium-， high-dose groups （6.825， 13.65， 27.3 g·kg-1） and Niaoduqing Granules group （2.6 g·kg-1）. The drug intervention groups received corresponding drugs by gavage for 8 consecutive weeks. After administration， hematoxylin-eosin （HE） staining and Masson staining were used to observe the morphological changes of rat renal tissue， and blood creatinine （SCr）， blood urea nitrogen （BUN） and blood uric acid （UA） were tested. Enzyme-linked immunosorbent assay （ELISA） was performed to detect the serum contents of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） and C-reactive protein （CRP）. The mRNA expressions of SOCS3 and TLR4 in renal tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expressions of SOCS3， TLR4， nuclear transcription factor （NF-κB） and myeloid differentiation factor （MyD88） were detected by Western blot. Immunohistochemistry was used to determine the protein expressions of NF-κB， MyD88， NOD-like receptor protein 3 （NLRP3） and melanoma deficiency factor 2 （AIM2）. ResultCompared with the sham group， the model group had a significant inflammatory response in renal tissue， and an increase in blood SCr， BUN， UTP， IL-6， TNF-α and CRP （P<0.05）. The protein and mRNA expressions of SOCS3 in renal tissue of rats in the model group were lower while the protein expressions of TLR4， NF-κB， MyD88， NLRP3 and AIM2 and the mRNA expression of TLR4 were higher than those in the sham group （P<0.05）. Compared with the model group， DHXZ and Niaoduqing granules groups presented markedly reduced inflammatory response in renal tissue and decreased blood SCr， BUN， UTP， IL-6， TNF-α and CRP （P<0.05）. Additionally， DHXZ and Niaoduqing granules up-regulated the protein and mRNA expressions of SOCS3 in renal tissue while down-regulated the protein expressions of TLR4， NF-κB， MyD88， NLRP3 and AIM2 and the mRNA expression of TLR4 （P<0.05）. ConclusionDHXZ can reduce the release and expression of inflammatory factors， inhibit the inflammatory response and improve renal function， and the mechanism may be related to the regulation of SOCS3/TLR4 signaling pathway.
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ObjectiveTo observe the effect of Hedysari Radix polysaccharide （HRP） on the Janus kinase 2 （JAK2）/signal transducer and activator of transcription protein 3 （STAT3） signaling pathway in diabetic nephropathy db/db mice. MethodFifty db/db mice were randomly divided into model group， irbesartan group （irbesartan suspension， 22.75 mg·kg-1）， and high-， medium-， and low-dose HRP groups （HRP suspension， 200， 100， 50 mg·kg-1） according to the body weight， with 10 mice in each group. Another 10 C57BL/6 mice were assigned to the normal group. The mice were treated with corresponding drugs by gavage， while those in the normal group and the model group received distilled water at 5 mL·kg-1. The mice in the six groups were administered once a day by gavage for 12 consecutive weeks. The uric acid （UA）， triglycerides （TG）， and total cholesterol （TC） were detected. Periodic acid-Schiff （PAS） staining and Masson staining were used to observe the pathological changes in kidney tissues. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to detect the protein and mRNA expression levels of JAK2， STAT3， suppressor of cytokine signaling 3 （SOCS3）， and tumor necrosis factor-α （TNF-α） in the kidney. ResultAfter 12 weeks of treatment， compared with the normal group， the model group showed significant pathological ultrastructural changes in kidney tissues and increased UA， TG， and TC levels （P<0.01）. Compared with the model group， the high- and medium-dose HRP groups and the irbesartan group showed improvement in pathological ultrastructure of kidney tissues and reduced UA， TG， and TC levels （P<0.05， P<0.01）. Compared with the normal group， the model group showed a decrease in SOCS3 protein and mRNA expression levels and an increase in JAK2， STAT3， and TNF-α protein and mRNA expression levels （P<0.01）. Compared with the model group， the high- and medium-dose HRP groups and the irbesartan group showed an increase in SOCS3 protein and mRNA expression levels and a decrease in JAK2， STAT3， and TNF-α protein and mRNA expression levels （P<0.05， P<0.01）. ConclusionHRP can alleviate renal damage in diabetic nephropathy to a certain extent， and its mechanism may be related to the inhibition of the activation of the JAK2/STAT3 signaling pathway.
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OBJECTIVE@#Rheumatoid arthritis (RA) progression is associated with the balance of T-regulatory (Treg) and T-helper 17 (Th17) cells, while the role of microRNAs (miRs) in regulating Treg/Th17 cell balance has not been clarified. This study aimed to assess whether moxibustion could regulate Treg/Th17 cell balance by modulating the miR-221/suppressor of cytokine signaling 3 (SOCS3) axis in the RA mouse model.@*METHODS@#A mouse model of collagen-induced arthritis (CIA) was established in male DBA/1J mice. Twenty-two days after CIA induction, the mice received daily treatment with moxibustion for 12 times. Pathological scores were assessed according to the levels of synovial hyperplasia. The expression levels of cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-17 and IL-10 were analyzed in serum by enzyme-linked immunosorbent assay. The cluster of differentiation 4 (CD4+) splenocytes was analyzed by fluorescence-activated cell sorting. The expression levels of RA-related miRs and target genes were subsequently detected, and the target of miR-221 was confirmed by the dual-luciferase reporter assay.@*RESULTS@#It was revealed that moxibustion treatment decreased the pathological scores and downregulated the expression levels of IL-1β, IL-6, TNF-α, IFN-γ and IL-17, while upregulated the expression level of IL-10. The Treg/Th17 cell balance was regulated by moxibustion treatment. The expression level of miR-221 was suppressed by moxibustion treatment. Furthermore, SOCS3 was found as the direct target of miR-221, which mediated the function of moxibustion by regulating the Treg/Th17 cell balance.@*CONCLUSION@#Moxibustion therapy regulated the Treg/Th17 cell balance by modulating the miR-221/SOCS3 axis in the RA mouse model.
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Animals , Male , Mice , Arthritis, Experimental/therapy , Arthritis, Rheumatoid/therapy , Cytokines , Disease Models, Animal , Interleukin-10 , Interleukin-17 , Interleukin-6 , Mice, Inbred DBA , MicroRNAs/genetics , Moxibustion , T-Lymphocytes, Regulatory , Th17 Cells/pathology , Tumor Necrosis Factor-alphaABSTRACT
OBJECTIVE: To investigate the effect of acupuncture plus moxibustion on learning-memory ability and expression of hippocampal Janus kinase-2 (JAK2)/signal transducer and activator of transcription-3 (STAT3)/suppressors of cytokine signaling-3 (SOCS3) signaling in Alzheimer's Disease (AD) rats, so as to reveal their mechanisms underlying improvement of AD. METHODS: A total of 60 SD rats were randomly divided into four groups：normal control, sham-operation, model and acupuncture-moxibustion (Acu-moxi, n＝15 in each group) groups. The AD model was established by microinjection of β-amyloid 1-42(Aβ1-42，5 µL)into the bilateral hippocampus. Seven days after modeling, Acu-moxi intervention was given. After insertion of acupuncture needles into "Baihui" (GV20) and bilateral "Shenshu" (BL23) and manipulating them for a while, the needles were then retained for 15 min, when, the mild moxibustion was performed at the same time. The treatment was conducted once daily, 5 times a week for consecutive 4 weeks. After the treatment, Morris water maze test was used to detect the animals' learning-memory ability. Immunohistochemistry and Western blot were respectively used to detect the number of positive cells and protein expression levels of JAK2, STAT3 and SOCS3 in the hippocampus tissue. RESULTS: Following modeling and compared with the normal control and sham-operation groups, the average escape latency was significantly prolonged (P<0.01), and the number of the original platform crossing and the residence time in the platform quadrant were significantly shortened in the model group (P<0.01). The numbers of hippocampal JAK2- and STAT3-positive cells and expression levels of hippocampal JAK2 and STAT3 proteins were significantly increased (P<0.01), and the number of hippocampal SOCS3-positive cells as well as the expression of SOCS3 protein significantly decreased in the model group relevant to the normal control and sham-operation groups (P<0.01). After the intervention, the average escape latency was significantly shortened (P< 0.01), and the number of the original platform crossing and the residence time in the platform quadrant were significantly increased in the Acu-moxi group (P<0.01), and the expression levels of JAK2 and STAT3 were significantly down-regulated and that of SOCS3 was considerably up-regulated in the Acu-moxi group relevant to the model group (P<0.01)．. CONCLUSION: Acu-moxi intervention can improve the learning-memory ability in AD rats, which is associated with its functions in inhibiting hippocampal JAK2/STAT3 signaling and up-regulating SOCS3 (a negative feedback factor) protein level.
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Objective To investigate the relationship among serum heat shock protein 70 (HSP70), suppressor of Cytokine Signaling-3 ( SOCS-3) and immune factor in pregnant women with hypertension,and to analyze the diagnostic value of the two indicators. Methods Eighty-six pregnant women with hypertension who were treated in the Second People′s Hospital of Yichang from January 2016 to February 2018 were selected,according to the severity of the disease,they were divided into pre-eclampsia (51 cases) and severe pre-eclampsia group (35 cases),another 40 normal pregnant women in the same period were selected as control group. The serum levels of HSP70 and SOCS-3,plasma immunoglobulin A (IgA), immunoglobulin M ( IgM), immunoglobulin G ( IgG), complement C3 and complement C4 levels were detected in each group,the correlation between serum HSP70 and SOCS-3 levels and immune factors were analyzed. ROC curve was used to analyze the predictive value of serum HSP70 and SOCS-3 in hypertensive disorder complicating pregnancy. Results The serum HSP70 of pre eclampsia and severe preeclampsia group was ( 3. 92 ± 0. 35 ) μg/L, the serum HSP70 of eclampsia group was ( 6. 45 ±0. 78) μg/L,which were significantly higher than that of the control group ( 0. 36 ± 0. 07) μg/L, the differences were statistically significant (t＝63. 272,49. 202,P＜0. 05),the serum SOCS-3 of pre eclampsia and severe preeclampsia group was (0. 22±0. 08) ng/L,the serum SOCS-3 of eclampsia group was (0. 10 ±0. 03) ng/L,which were significantly lower than ( 0. 62 ± 0. 11) ng/L that of the control group ( 0. 62 ±0. 11) ng/L,the differences were statistically significant (t＝－20. 078,－27. 079,P＜0. 05),the serum HSP70 of eclampsia group was significantly higher than that of the pre eclampsia and severe preeclampsia group,the difference was statistically significant (t＝－20. 402,P＜0. 05),the serum SOCS-3 of eclampsia group was significantly lower than that of the pre eclampsia and severe preeclampsia group,the difference was statistically significant ( t＝8. 462, P＜0. 05) . The plasma IgM was ( 1. 83 ± 0. 56) g/L, IgG was ( 7. 94 ±1. 34) g/L,complement C3 was (0. 95±0. 08) g/L,complement C4 was (0. 24±0. 08) g/L in the pre eclampsia and severe preeclampsia group, the plasma IgM was ( 1. 42 ± 0. 58 ) g/L, IgG was ( 5. 23 ±1.13) g/L,complement C3 was (0.73±0.12) g/L,complement C4 was (0.13±0.05) g/L in the eclampsia group,the plasma IgM was (2. 55±0. 53) g/L,IgG was (11. 04±2. 15) g/L,complement C3 was (1. 28 ±0. 15) g/L,complement C4 was (0. 35±0. 08) g/L in the control group (IgM:t＝－6. 232,－8. 815, P＜0. 05;IgG: t＝－8. 426,－14. 340, P＜0. 05; C3: t＝－13. 470,－17. 364, P＜0. 05; C4: t＝－6. 510,－14. 040,P＜0. 05),the plasma levels of IgM,IgG,complement C3 and complement C4 in eclampsia group were significantly lower than those in pre eclampsia and severe preeclampsia group ( t＝3. 288,－9. 805, 10. 209,7. 217,P＜0. 05). Pearson correlation analysis showed,there was a negative correlation among serum HSP70 and plasma IgM,IgG,complement C3 and complement C4 in hypertensive women with gestational hypertension (r＝－0. 446,－0. 537,－0. 426,－0. 428,P＜0. 05),serum SOCS-3 was positively correlated with plasma IgM,IgG,complement C3 and complement C4 (r＝0. 423,0. 507,0. 416,0. 407,P＜0. 05),there was no correlation among serum HSP70, SOCS-3 and plasma IgA in pregnant women with hypertension ( r＝－0. 082,0. 093,P＞0. 05). The area under the ROC curve of HSP70 was 0. 821,and the critical value of the prediction was more than 0. 89 μg/L,the sensitivity of HSP70 to pregnant women with hypertension was 86. 3%,the specificity was 76. 4%,the area under the ROC curve of SOCS-3 was 0. 759,the critical value of the prediction was less than 0. 035 ng/L,and the sensitivity of SOCS-3 to pregnant women with hypertension was 79. 4%,and the specificity was 71. 6%. Conclusion The abnormal increase of serum HSP70 and abnormal decrease of SOCS-3 in pregnant women with hypertension, maternal serum HSP70 and SOCS-3 levels are closely related to immune factors,the serum HSP70 and SOCS-3 may be used as early predictors of hypertensive disorder complicating pregnancy.
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Objective To evaluate the role of suppressor of cytokine signaling 3 ( SOCS3) in the spinal cord of chronic sciatic constriction injury ( CCI) mice. Methods Part one:four Kunming mice were selected to receive the CCI operation by sciatic nerve ligation. Seven days after operation the mice were sac-rificed and L4～6 segments of the spinal cord were removed. The co-expression of SOCS3 with NeuN ( for neurons),GFAP (for astrocytes),or IBA1 (for microglia) in spinal were detected by immunohistofluores-cence. Part two:thirty-two Kunming mice were divided into 4 groups according to random number table:sham operation group (group SH),CCI group (group BP),CCI+Lenti-SOCS3 group (group BS),CCI +Lenti-vector group (group BV). Group BS were intrathcal injected of Lenti-SOCS3 (2 μl) and group BV were intrathcal injected of Lenti-vector (2 μl) on 7 d,8 d,9 d after operation. Paw withdrawal latency ( PWL) and paw withdrawal threshold ( PWT) were measured at 1 d before operation and 5,7,10,12,14 d after operation. Mice were then sacrificed and L4～6 segments of the spinal cord were removed for determina-tion of GFAP,IBA-1 by Western blot and IL-6,IL-1β,TNF-α by Elisa on 14 d. Results SOCS3 was dis-tributed in dorsal horn,and expressed in astrocytes and microglia,but hardly colocalized with neurons. Com-pared with group SH,the PWL and PWT of group BP and BV were significantly decreased after operation (all P<0. 05),and the expression of GFAP,IBA-1,IL-6,IL-1β and TNF-α was significantly increased (all P<0. 05). Compared with group BV,the PWL (5. 1±0. 9,7. 5±0. 8,7. 2±1. 4) and PWT (6. 1±1. 4,8. 9± 1. 1,8. 2±2. 1) of group BS was significantly increased on 10,12,14 d (all P<0. 05),and the expression of GFAP (1. 69±0. 45),IBA-1(1. 76±0. 25),IL-6 (181±8),IL-1β (151±7),TNF-α (216±9) was signifi-cantly downregulated (P<0. 05) . Conclusion SOCS3 alleviates neuropathic pain by inhibiting the glial ac-tivation and the expression of proinflammatory cytokines IL-6,IL-1β,TNF-α.
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Interleukin-6(IL-6)is a pleiotropic cytokine with central roles in immune and inflammatory reactions through downstream activation of the Janus kinase 2/signal transducer and activator of transcription 3 /Suppressor of cytokine signaling3 ( JAK/STAT3/SOCS3 ) signaling pathway. Additionally, dysregulation of the interleukin( IL)-6-mediated JAK/STAT3/SOCS3 signaling pathway is closely related to the development of in-flammatory bowel disease( IBD) . On this basis,modulation of the IL-6/JAK/STAT3/SOCS3 signaling pathway is currently being widely explored to develop novel therapies for IBD. The present review details the mechanisms and roles of the IL-6/JAK/STAT3/SOCS3 pathway in IBD, describes current therapeutic strategies, and the search for potential therapeutic approaches to treat IBD.
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Interleukin-6(IL-6)is a pleiotropic cytokine with central roles in immune and inflammatory reactions through downstream activation of the Janus kinase 2/signal transducer and activator of transcription 3 /Suppressor of cytokine signaling3 ( JAK/STAT3/SOCS3 ) signaling pathway. Additionally, dysregulation of the interleukin( IL)-6-mediated JAK/STAT3/SOCS3 signaling pathway is closely related to the development of in-flammatory bowel disease( IBD) . On this basis,modulation of the IL-6/JAK/STAT3/SOCS3 signaling pathway is currently being widely explored to develop novel therapies for IBD. The present review details the mechanisms and roles of the IL-6/JAK/STAT3/SOCS3 pathway in IBD, describes current therapeutic strategies, and the search for potential therapeutic approaches to treat IBD.
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Objective To investigate the effect of suppressor of cytokine signaling 3 (SOCS3)on the proliferation of human mesangial cells stimulated by aggregated IgA1 (aIgA1) from patients with IgA nephropathy(IgAN),and explore its possible mechanism.Methods Serum monomeric IgA1 was isolated with jacalin affinity and Sephacryl S-200 HR chromatography from IgAN patients,and then heated to aggregated form (aIgA1).Human glomerular mesangial cells(HMC) were transfected with AdvSOCS3-IRES2-EGFP for 48 hours,and incubated with aIgA1 for 12-48 h.The cells were divided into blank control group,IgA1 group,IgA1 +Adv-EGFP group and IgA 1 +Adv-SOCS3-IRES2-EGFP group.The mesangial cell proliferation was observed through MTT,and the levels of SOCS3,TLR4,TGF-β1 protein and mRNA were detected through Western blotting and real-time PCR.Results HMC proliferation was promoted significantly after IgA1 stimulated at 24 h.Compared with control group,the protein and mRNA expression of SOCS3,TLR4,TGF-β1 were significantly increased in IgA1 group (P ＜ 0.05).Compared with IgA1 group and IgA1 +Adv-EGFP group,MTT absorbency was obviously reduced after incubation with aIgA1 for 24 h and 48 h in IgA+Adv-SOCS3-IRES2-EGFP group,and the protein and mRNA expression of TLR4 and TGF-β1 were significantly decreased in IgA1 +AdvSOCS3-EGFP group (P＜ 0.05).Conclusion Over-expression of SOCS3 may inhibit the proliferation of HMC stimulated by aIgA1,partly through down-regulating the expression of TLR4 and TGF-β1.
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AIM:To investigate the effects of glucagon-like peptide-1 (GLP-1) on mRNA expression of SOCS-3 and SREBP-1c in the rats with nonalcoholic fatty liver disease.METHODS:Male SD rats were randomly divided into normal control ( NC) group, high fat ( HF) group and HF+liraglutide ( Lira) group.The rats in HF group and HF+Lira group were given high-fat diet for 16 weeks.After 12 weeks of high-fat diet feeding in HF+Lira group, Lira (600μg? kg-1? d-1 ) was intraperitoneally injected for 4 weeks.At the end of the 16th week, the rats were killed.The pathologi-cal changes of the liver were observed under optical microscope.The serum levels of alanine aminotransferase ( ALT) , as-partate aminotransferase ( AST) , triglyceride ( TG) and total cholesterol ( TC) were detected by automatic biochemical an-alyzer.TG contents of liver were measured by GPO-PAP method.The fasting insulin ( FINS) was determined by ELISA, and insulin resistance index was assessed by homeostasis mode assessment ( HOMA-IR) .The mRNA expression of SOCS-3 and SREBP-1c in the liver tissues was detected by RT-qPCR.RESULTS:Compared with NC group, HOMA-IR, TG of liver, and the serum levels of ALT, AST, TG, TC and FINS in HF group were obviously increased (P duce TG of liver through decreasing the mRNA expression of SOCS-3 and SREBP-1c, so as to play a therapeutic role in nonalcoholic fatty liver disease.
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Objective:To study the influence of miR-221 in theβcells of mice with diabetic nephropathy (DN), and to clarify the protective effect of miR-221 on DN.Methods:Twenty wild type C57BL/6J mice aged 8 weeks were divided into control group and DN group (n=10).The DN mice models were constructed with 14 weeks of high fat diet,and 100 mg·kg-1 streptozotocin (STZ)was used to induce the partial insulin deficiency.10 weeks later the blood glucose,serum creatinine,blood urea nitrogen content and 24h-urinary albumin excretion rate were detected.Theβcells of islet were isolated from the DN mice.The expression level of SOCS3 mRNA inβ cells of islet was valued by Real-time PCR.The proliferation of pancreaticβcells of islet was examined by MTT assay.The contents of insulin and insulin release levels in pancreaticβ cells of islet were detected by ELISA assay.Luciferase reporter gene assay was used to detect the luciferase reporter gene activity of SOCS3.Results:The DN mouse models were constructed successfully.The blood glucose,serum creatinine,blood urea nitrogen and 24h-urinary albumin excretion rate of the mice in DNA group were higher than those in control group (P < 0.05 ).After overexpression of miR-221,the expression level of SOCS3 mRNA in pancreaticβcells of islet and the proliferation ability ofβcells of islet of the mice in DN group were lower than those of normal islet cells (P < 0.05).Then luciferase reporter gene method found SOCS3 as one of the target genes of miR-221.After overexpression of miR-221,the insulin release level and insulin content in pancreaticβcells of islet were higher than those of normal islet cells (P <0.05).Conclusion:miR-221 can promopt the synthesis and secretion ofβ cells of islet and inhibit the dysfunction ofβcells of islet in the DN mice by down-regulating the SOCS3 level.
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Objective To study the expression of signal transducer and activator of transcription 3 (STAT3) and Suppressor of cytokine signaling 3(SOCS3) in the middle ear cholesteatoma epithelium ,and the possible roles of STAT3 and SOCS3 in middle ear cholesteatoma .Methods The immunohistochemical assay was used to detect ex-pression of STAT3 and SOCS3 protein in 30 cases of middle ear cholesteatoma epithelial tissue and 20 cases of nor-mal external auditory canal skin tissues as the control group .Results STAT3 immunoreactivity was detected in the nuclei and cytoplasm of epithelial cells .The expression rates of STAT3 in middle ear cholesteatoma epithelial tissue were 76 .7% and higher than in the normal epithelium (25 .0% ) .The differences between the two groups were sta-tistically significant (P<0 .05) .SOCS3 immunoreactivity was detected in the cytoplasm of epithelial cells .The ex-pression rates of SOCS3 in middle ear cholesteatoma epithelial tissue were 33 .3% and lower than in the normal epi-thelium (65 .0% ) .The differences were statistically significant (P<0 .05) .The expression of STAT3 and SOCS3 in the middle ear cholesteatoma had negative correlation (r= - 0 .476 ,P<0 .05) .Conclusion The abnormal ex-pression of STAT3 and SOCS3 in the middle ear cholesteatoma may be involved in hyper proliferation and anti -ap-optosis of cholesteatoma cell ,and play an important role in the formation and development of middle ear cholesteatoma .
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Objective To investigate the levels of activated Stat3 (p‐Stat3) and the expression levels of SOCS3 as well as their clinical significance and its impact on the pathogenesis ,progression ,and prognosis in patients with gastric cancer .Methods The levels of p‐Stat3 and SOCS3 were tested in 53 cases of gastric cancer tissues (test group) and 27 cases of adjacent non cancerous tis‐sues (control group) by immunohistochemistry (IHC) .The clinical pathological and follow up data were analyzed .Results The levels of activated p Stat3 were significantly higher in gastric cancer tissues than in non cancerous tissues .The levels of SOCS3 were lower in cancer tissues than in non cancerous control tissues (P<0 .05) .p‐Stat3 showed significantly different levels among TNM stages and tumor differentiation ,and the expression levels of SOCS3 were negatively associated with cancer invasion ,lymph node metastasis and TNM stages in cancer patients (P<0 .05) .Furthermore ,a negative correlation was observed between the levels of activated p‐Stat3 and SOCS3 in gastric cancer tissues (r= -0 .492 ,P<0 .05) .Kaplan Meier survival analyses indicated that the p‐tat3 levels were negatively correlated with total survival of gastric cancer patients ,the higher the levels of p‐Stat3 was ,the lower the total survival rate would be (χ2 = -5 .05 ,P<0 .05) .On the contrary ,the levels of SOCS3 showed a positive correlation with total survival (χ2 =10 .852 ,P<0 .05) .Conclusion Increased a p‐Stat3 and decreased expression of negative Stat3 regulator SOCS3 may play important roles in the development and progression of gastric cancer ,both of which would potentially serve as prognostic mark‐ers for gastric cancer .
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Objective To investigate the relationship between SOCS-3 gene polymorphism and abnormal glucose metabolism in Xinjiang Uygur population.Methods According to different plasma glucose levels,1232individuals in Xinjiang Hetian area were divided into 3 groups,451 patients with pre-diabetes,252 patients with type 2 diabetes mellitus,and 529 healthy people as normal controls.Based on HapMap,the polymorphisms rs12953258,rs4969168,rs9914220 were selected as haplotypes,tagging SNP (htSNP) sufficiently covering the genetic variation of the whole gene.Associations of rs12953258,rs4969168,and rs9914220 within SOCS-3 with abnormal glucose metabolism in three groups of Xinjiang Uygur population were examined ; The genotype and allele frequencies and relative clinic data were compared among groups.Results The type 2 diabetes mellitus study with 451 individuals showed that the homozygosity for the C allele of rs12953258 polymorphism of SOCS-3 was associated with increased diabetes risk(OR=1.756,95％ CI 1.168-2.640).In addition,association between rs4969168 or rs9914220 and abnormal glucose metabolism in the Xinjiang Uygur population was not found.Age,total cholesterol,and body mass index were risk factors of diabetes mellitus,total cholesterol and low high density lipoprotein-cholesterol were risk factors of pre-diabetes in Uygur people.Conclusions The C allele of rs12953258 polymorphism of SOCS-3 gene may be an independent risk factor for abnormal glucose metabolism in Xinjiang Uygur population.
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ObjectiveTo investigate whether hypothalamic silencing of suppressor of cytokine signaling 3( SOCS3 ) by RNA interference ( RNAi ) attenuates diet-induced obesity and leptin resistance in rats.Methods Hypothalamic SOCS3-deficient rats were established by means of lentiviral vector ( LV ) mediated RNAi technique,and then were fed with a high-fat diet for 8 weeks.After the rats were sacrificed,the serum leptin and insulin concentrations were measuredbyRIA, andthe expressionof SOCS3inhypothalamus was detectedby immunohistochemistry and realtime PCR.ResultsThe immunostaining showed that SOCS3 protein expression was significantly reduced and the expression of SOCS3 mRNA was decreased by 49％ in SOCS3 RNAi group compared to the controls( P＜0.01 ).The rats with hypothalamic SOCS3 knockdown exhibited a significant hampering in gaining body weight with lowered concentrations of leptin[ ( 8.18±2.10 vs 10.85±2.23 ) ng/ml ],insulin[ ( 18.89±4.88 vs 26.78±6.01 )mU/L],glucose [ (4.89±0.91 vs 6.26± 1.41 )mmol/L] and triglyceride [ (0.47 ±0.10 vs 0.62 ±0.16)mmol/L] when exposed to a high-fat diet(P＜0.05 or P＜0.01 ).ConclusionThe results provide evidence that rats with hypothalamic SOCS3 silencing by RNAi are resistant to diet-induced obesity,leptin resistance,and metabolic disorder.
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BACKGROUND:As the regulators of cytokines, suppressors of cytokine signaling (SOCS) play an important role in the inflammation reaction. Some studies found that SOCS-1 and SOCS-3 were involved in the pathogenesis of some inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease. But the expressions of SOCS in coronary heart disease have not yet been reported. This study aimed to investigate the expression and clinical significance of SOCS-1 and SOCS-3 in the myocardium of patients with sudden cardiac death (SCD).METHODS:Myocardial autopsy specimens were collected from 24 patients at the Forensic Medicine Department of Sun Yat-Sen University, Guangzhou, China between 2005 and 2006. Of them, 9 patients had autopsy findings consistent with coronary atherosclerosis (non-myocardial infarction) leading to SCD (non-MI group), 7 died of acute myocardial infaction (MI group), and 8 died from traffic accidents and trauma (control group). The expressions of SOCS-1 mRNA and SOCS-3 mRNA in the myocardium of the non-MI, MI and control groups were detected using RT-PCR. The levels of SOCS-1 and SOCS-3 proteins were detected using immunohistochemistry. Statistical analyses were performed using SPSS version 13.0 software and the data were analyzed by ANOVA.RESULTS:The expressions of SOCS-1 mRNA and SOCS-3 mRNA in the non-MI and MI groups were significantly higher than those in the control group[(0.788±0.101), (0.741±0.111) vs. (0.436±0.044), (P<0.01); (0.841±0.092), (0.776±0.070) vs. (0.454±0.076), (P<0.01)] respectively. The antibody-positive cells of SOCS-1 protein in the myocardium of the non-MI and MI groups were significantly higher than those in the myocardium of the control group[(320.00±48.48), (347.14±70.88) vs. (42.50±10.35), (P<0.01)] respectively. The antibody-positive cells of SOCS-3 protein in the myocardium of the non-MI and MI groups were significantly higher than those in the myocardium of the control group[(381.11±59.25) vs. (40.00±10.69), (P<0.01)] and[(332.86±111.91) vs. (40.00±10.69), (P=0.001)].CONCLUSION:The expressions of SOCS-1 and SOCS-3 in the myocardium of patients with SCD from coronary heart disease are significantly increased and contribute to the pathogenesis of SCD.
ABSTRACT
Objective To investigate the expressions and clinical significanees of suppressors of cytokine signaling-1 (SOCS-1) and SOCS-3 in myocardium of patients with sudden cardiac death (SCD). Method This study included myocardial autopsy specimens of 24 patients admitted between 2005 and 2006. Of them, 9 cases had the findings of autopsy examination consistent with coronary atberosclerosis (non-myocardial infarction) leading to SCD (non-MI group), 7 patients died of acute myocardial infarction (MI group) and 8 patients died of traffic accidents and trauma The expressions of SOCS-1 mRNA and SOCS-3 mRNA in the myocardium of non-MI and con-trol group were detected by using RT-PCR. The levels of SOCS-1 protein and SOCS-3 protein were detected by us-ing immunohistochemistry. Statistical analysis were performed by using SPSS version 13.0 software and the data were processed with ANOVA test. Results The expressions of SOCS-1 mRNA and SOCS-3 mRNA in non-MI and MI groups were were significantly higher than those in control group (0. 788±0. 101) and (0. 741±0.111) vs.(0.436±0.044) (P <0.01); (0.841±0.092) and (0.776±0.070) vs.(0.454±0.076), P <0.01, re-spectively). The antibody-positive cells of SOCS-1 protein in myocardium of non-MI group and MI group were significantly higher than those in myoeardium of control group (320.00±48.48) and (347.14±70.88) vs.(42.50±10.35) (P < 0.01), respectively. The antibody-positive cells of SOCS-3 protein in myoeardium of non-MI group and MI group were significantly higher than those in myocardium of control group (381.11±59.25) vs.(40.00±10.69), (P < 0.01)and (332.86±111.91) vs. (40.00±10.69), (P =0.001). Conclusions The expressions of SOCS rnRNA and SOCS-3 mRNA in myoeardium of patients with SCD from coronary diseases are significantly increased contributing to the pathogenesis of SCD.
ABSTRACT
Suppressor of cytokine signaling (SOCS)-3 is a negative regulator of interleukin (IL)-6 signal transduction. The results showed that IL-6 was not only correlated with insulin resistance but also capable to induce the expression of SOCS-3.Thus the high expression of SOCS-3 mRNA may contribute to one of the mechanisms of IL-6 dependent insulin resistance.