Secreted modular calcium-binding proteins in pathophysiological processes and embryonic development / 中华医学杂志(英文版)

Objective@#Secreted modular calcium-binding proteins (SMOCs) are extracellular glycoproteins of the secreted protein, acidic, and rich in cysteine-related modular calcium-binding protein family and include two isoforms, SMOC1 and SMOC2, in humans. Functionally, SMOCs bind to calcium for various cell functions. In this review, we provided a summary of the most recent advancements and findings of SMOC1 and SMOC2 in development, homeostasis, and disease states.@*Data sources@#All publications in the PubMed database were searched and retrieved (up to July 24, 2019) using various combinations of keywords searching, including SMOC1, SMOC2, and diseases.@*Study selection@#All original studies and review articles of SMOCs in human diseases and embryo development written in English were retrieved and included.@*Results@#SMOC1 and SMOC2 regulate embryonic development, cell homeostasis, and disease pathophysiology. They play an important role in the regulation of cell cycle progression, cell attachment to the extracellular matrix, tissue fibrosis, calcification, angiogenesis, birth defects, and cancer development.@*Conclusions@#SMOC1 and SMOC2 are critical regulators of many cell biological processes and potential therapeutic targets for the control of human cancers and birth defects.

Expression of SPARC in smooth muscle tissue of ob/ob mice and its clinical significance / 中国基层医药

Objective To investigate the secreted protein acidic and rich in cysteine (SPARC) expression in the smooth muscle tissue of ob/ob mice.Methods Study time:February 2017 to June 2017.Six ob/ob mice and 6 littermates aged 10 weeks were selected for the trial.The mesenteric artery smooth muscle tissues were collected.qRT -PCR was used to detect SPARC mRNA expression in smooth muscle tissue.The protein expression of SPARC was assayed by Western blot.Results The SPARC mRNA [(1.73 ± 0.65)] and protein [(1.73 ± 0.65)] in smooth muscle tissue of ob/ob mice presented higher expression compared with those in the littermates [(1.00 ± 0.31),(1.00 ± 0.33),t =8.437,5.533,all P ＜ 0.05].Conclusion The higher expression of SPARC in smooth muscles tissue of ob/ob mice may be involved in diabetes combined with atherosclerosis.

Silencing SPARC inhibits high fluoride-induced apoptosis of thyrocytes / 西安交通大学学报(医学版)

Objective: To investigate the effects and mechanisms of secreted protein, acidic and rich in cysteine (SPARC) on high fluoride-induced apoptosis of thyrocytes. Methods: Human thyroid cells (Nthy-ori 3-1) were cultured and treated with various concentrations (0.1, 1 and 10 mmol/L) of NaF for 24 h, and the expression of SPARC was evaluated using Real-time PCR and Western blot, respectively. The cells were divided into four groups: control group, NaF group, si-SPARC group (cells were transfected with SPARC siRNA for 48 h and then exposed to NaF for 24 h), and si-NC group (cells were transfected with negative control siRNA for 48 h and then exposed to NaF for 24 h). Cytotoxicity was assayed using CCK-8 and LDH; cell apoptosis rate was detected with ELISA. The expressions of cleaved caspase3 (c-caspase3) and IGF-1R were measured by Western blot. In addition, si-SPARC and si-IGF-1R were co-transfected into thyrocytes to further explore mechanisms of SAPRC by evaluating apoptosis. Results: The mRNA and protein levels of SPARC were augmented with the increase of NaF (P<0.05). Cell viability was significantly higher in si-NC group than that in si-SPARC group [(84.02±9.51)% vs. (58.31±6.86)%, P<0.05], and the release rate of LDH was lower [(134.25±18.98)% vs. (195.18±23.50)%, P<0.05]. Cell apoptosis rate was lower in si-SPARC group than that in si-NC group [(124.67±19.44)% vs. (175.24±16.46)%, P<0.05]. In addition, silencing SPARC upregulated the expression of IGF-1R (1.95±0.24 vs. 0.93±0.08, P<0.05), and inhibition of IGF-1R reversed the effect of SPARC on apoptosis. Conclusion: Inhibition of SPARC reduces high fluoride-induced cytotoxicity and blocks cell apoptosis. The possible mechanism is through the negative regulation of IGF-1R.

Research progress of secreted protein acidic and rich in cysteine in glaucoma filtering bleb scarring / 上海交通大学学报（医学版）

Filtering bleb scarring is the main cause of glaucoma filtration surgery failure. Subconjunctival injection of antimetabolites, such as mitomycin and 5-fluorouracil, is widely used clinically to reduce the incidence of scarring, which improves the success rate of the surgery. However, accompanied side effects such as cytotoxicity should not be ignored. Secreted protein acidic and rich in cysteine (SPARC) as a matricellular protein is widely distributed in the eyes, which plays an important role in the process of wound repairing and tissue remodeling. The expression of SPARC is significantly elevated in the mouse model of subconjunctival scarring. Researches suggest that SPARC participates in and regulate the formation of bleb scarring through multiple pathways, therefore it may become a specific new target in the anti-scarring therapy.

Effects of vascular endothelial growth factor on the fibrosis and the expression of secreted protein acidic and rich in cysteine in cultured human Tenon's fibroblast / 上海交通大学学报（医学版）

Objective:To investigate the effects of vascular endothelial growth factor (VEGF) on the expression of secreted protein acidic and rich in cysteine (SPARC) and the fibrosis in cultured human Tenon's fibroblast (HTF) in vitro. Methods:HTF cells were obtained from Tenon's capsule tissues of patients undergoing strabismus surgery. Immunofluorescence was used to identify the HTF cells. HTF cells were cultured with different concentrations of VEGF, and which were divided into four groups, i.e., 0 ng/mL group, 25 ng/mL group, 50 ng/mL group and 100 ng/mL group. The expression of SPARC, collagen- , and matrix metalloprotein 9 (MMP-9) and the activity of extracellular signal-regulated kinase (ERK) pathway were analyzed by Western blotting and real-time quantitative PCR (qPCR). The abilities of proliferation and migration of HTF cells were detected by MTS assay and scratch test, respectively. Results:HTF cells were observed and identified by inverted phase contrast microscope and immunofluorescence. Under the stimulation of VEGF, the expression of protein and mRNA of SPARC, collagen-I and MMP-9 of HTF cells in other three groups were increased compared with 0 ng/mL group; the phosphorylation activities of ERK pathway were up-regulated, and the proliferation and migration abilities of HTF cells were up-regulated. And the effect was the most obvious in the 50 ng/mL group. Conclusion:VEGF is involved in promoting the fibrosis of HTF cells accompanied by the up-regulation of the SPARC, which suggests SPARC may become a potential regulatory site.

Secreted protein acidic and rich in cysteine (SPARC) induces epithelial-mesenchymal transition, enhancing migration and invasion, and is associated with high Gleason score in prostate cancer / 亚洲男科学杂志(英文版)

Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein highly expressed in bone tissue that acts as a chemoattractant factor promoting the arrival of prostate cancer (PCa) cells to the bone marrow. However, the contribution of SPARC during the early stages of tumor progression remains unclear. In this study, we show that SPARC is highly expressed in PCa tissues with a higher Gleason score. Through stable knockdown and overexpression of SPARC in PC3 and LNCaP cells, respectively, here we demonstrate that endogenous SPARC induces the epithelial-mesenchymal transition (EMT), decreasing E-cadherin and cytokeratin 18 and increasing N-cadherin and vimentin. Moreover, SPARC induces the expression of EMT regulatory transcription factors Snail family transcriptional repressor 1 (Snail), Snail family transcriptional repressor 2 (Slug), and zinc finger E-box binding homeobox 1 (Zeb1). In addition, SPARC knockdown in PC3 cells decreases migration and invasion in vitro, without modifying cell proliferation. Our results indicate that SPARC might facilitate tumor progression by modifying the cellular phenotype in cancer cells.

Secreted protein acidic and rich in cysteine (SPARC) induces epithelial-mesenchymal transition, enhancing migration and invasion, and is associated with high Gleason score in prostate cancer / 亚洲男科学杂志(英文版)

Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein highly expressed in bone tissue that acts as a chemoattractant factor promoting the arrival of prostate cancer (PCa) cells to the bone marrow. However, the contribution of SPARC during the early stages of tumor progression remains unclear. In this study, we show that SPARC is highly expressed in PCa tissues with a higher Gleason score. Through stable knockdown and overexpression of SPARC in PC3 and LNCaP cells, respectively, here we demonstrate that endogenous SPARC induces the epithelial-mesenchymal transition (EMT), decreasing E-cadherin and cytokeratin 18 and increasing N-cadherin and vimentin. Moreover, SPARC induces the expression of EMT regulatory transcription factors Snail family transcriptional repressor 1 (Snail), Snail family transcriptional repressor 2 (Slug), and zinc finger E-box binding homeobox 1 (Zeb1). In addition, SPARC knockdown in PC3 cells decreases migration and invasion in vitro, without modifying cell proliferation. Our results indicate that SPARC might facilitate tumor progression by modifying the cellular phenotype in cancer cells.

Expression and role of SPARCL1 gene in tumor / 国际肿瘤学杂志

Abnormal expression of secreted protein acidic and rich in cysteine like 1 (SPARCL1 )gene is closely related to the development,metastasis and prognosis of a variety of tumors.Recent studies show that SPARCL1 gene is high expressed in glioma.The protein product of SPARCL1 gene encoded can interact with collagen,thus affecting the metastasis ability of tumor,which is positively correlated with tumor malignant de-gree.SPARCL1 gene is low expressed in gastric cancer,colorectal cancer,prostate cancer and breast cancer, which is negatively correlated with the invasion and metastasis abilities of tumors.At present,the role of speci-fic molecular mechanisms of SPARCL1 gene remains controversial. The expressions and functions of SPARCL1 gene in tumor tissues seem to depend on the tumor microenvironment.

The research progression of SPARC with obesity and obesity-related disease / 医学研究生学报

Obesity and obesity-related diseases have become the main threat to human health .Acid secreted proteins that are rich in cysteine mainly derived from fat tissue , and are associated with insulin resistance , diabetes and diabetic nephropathy .This re-view summaries molecular biology features such as resistance of cell adhesion , regulating cell proliferation , tissue differentiation and embryonic development and the latest research progress of its role in the obesity and obesity related diseases .

Effect of aconitine on serum zinc finger protein 41 and SPARC in ventricular septal defect model rats / 中国生化药物杂志

Objective To explore the effect of aconitine on serum zinc finger protein 41 and secreted protein acidic and rich in cysteine in ventricular septal defect model rats.Methods 80 ventricular septal defect model rats were randomly divided into two groups, experimental group ( n=40) were treated with 0.05 mg/kg aconitine via tail vein injection for 7 consecutive days;control group (n=40) were treated with normal saline via tail vein injection for 7 consecutive days.Then, the abdominal aorta blood of each rat was collected, and the contents of zinc finger protein 41 and SPARC in two groups were detected by Western blot and ELISA method,seperately.Results Western blot results showed that the expression of zinc finger protein 41 and SPARC in serum samples of experimental group were significantly lower than that of control group ( P<0.05 ) .ELISA results showed that the contents of zinc finger protein 41 and SPARC of experimental group was significantly lower than that of control group ( P<0.05 ), respectively.Conclusion Aconitine can decrease the expression of serum zinc finger protein 41 and SPARC in ventricular septal defect model rat.

Variations of SPARC levels in serum and foot muscle tissue of patients with type 2 diabetic foot / 中华内分泌代谢杂志

Objective To observe secreted protein acidic and rich in cysteine (SPARC) levels in serum and foot muscle tissue of patients with type 2 diabetic foot (DF).Methods All participants were divided into four groups with 40 cases in each group, including type 2 diabetic patients without (DMA) and with (DMB) lower limb arterial sclerosis and peripheral neuropathy, DF group, and normal control (NC) group.The muscle tissues of foot from DF group (n =6) and NC group (n =6) were taken.Serum SPARC level was measured with ELISA.RT-PCR, Western blot, immunofluorescence, and immunohistochemistry were used to examine SPARC mRNA and protein expressions in the foot muscle.Results Serum SPARC levels were higher in DMA and DMB groups compared with NC and DF groups[(1 040.48 ±212.12 and 1 068.36 ± 165.45 vs 841.93 ± 144.57 and 835.43 ± 188.37) ng/L, P＜ 0.01].There was no significant difference in serum SPARC level between DF and NC groups or DMA and DMB groups (P＞0.05).The expression levels of SPARC mRNA and protein in the foot muscle were higher in DF compared with NC group (P＜0.05).Conclusion SPARC mRNA and protein expressions in foot muscle tissue are higher in DF group compared with control group, indicating that SPARC may participate in the repair and healing of damaged muscle tissue of diabetic foot.

Variations of SPARC in obese patients with type 2 diabetes mellitus / 中华内分泌代谢杂志

Objective To observe serum secreted protein acidic and rich in cysteine (SPARC) levels in normal subjects,obese subjects,patients with type 2 diabetes mellitus (T2DM),and obese patients with T2DM,as well as the difference of SPARC expression in mesenteric adipose tissue of subjects with and without T2DM.Methods Serum SPARC level was measured with the ELISA.RT-PCR,Western blot,and immunofluorescence were used to examine SPARC mRNA and protein expressions in mesenteric adipose tissue.Results (1) SPARC levels were higher in obesity,T2DM,and T2DM with obesity groups compared with normal group [(1 191.6 ± 718.91,1 223.81 ± 645.96,1 538.01 ± 757.95 vs 851.07 ± 280.21) ng/L,P＜0.05].(2) Pearson correlation analysis showed that SPARC level was positively correlated with homeostasis model assessment for insulin resistance index (r =0.205,P＜ 0.05).(3) The expression levels of SPARC mRNA and protein in mesenteric adipose tissue of T2DM patients were higher than those of control subjects (P ＜ 0.05).Conclusion SPARC is closely related to the development of obesity,insulin resistance,and type 2 diabetes mellitus.

Correlation of secreted protein acidic and rich in cysteine with diabetic nephropathy / 中华内分泌代谢杂志

Objective To investigate the serum concentrations of secreted protein acidic and rich in cysteine (SPARC) in patients with diabetic nephropathy and SPARC mRNA and protein expressions in renal tissue of db/db mice.Methods Serum SPARC levels in normal subjects and patients with type 2 diabetes mellitus (without diabetic nephropathy),chronic renal failure (without diabetes mellitus),and diabetic nephropathy were determined with enzyme-linked immunosorbent assay.RT-PCR,Western blot,and immunofluorescence were used to detect the mRNA and protein expressions of SPARC in renal tissue of db/db mice.Results The serum level of SPARC in diabetic nephropathy group was significantly higher than those in normal group,type 2 diabetes mellitus,and chronic renal failure group [(5.78 ± 1.41 vs 3.58 ±0.41,4.51 ± 1.08,and 3.81 ± 1.16) μg/L,P＜0.05 or P＜0.01].The SPARC level in the type 2 diabetes mellitus group was higher than that in normal group (P＜0.05),but there was no difference between normal group and chronic renal failure.SPARC mRNA and protein levels in renal tissue of db/db mice were higher compared with the littermates (P ＜ 0.05).Conclusions The long term hyperglycemic state in patients with diabetic nephropathy causes pathological change of renal tissue.Simultaneously,increased secretion of SPARC from renal tissue results in elevation of serum SPARC level and may play a role in pathological change of diabetic nephropathy.

Effects of recombinant human parathyroid hormone (1-34) and elcatonin on bone metabolism and serum SPARC in postmenopausal women with osteoporosis / 中华内分泌代谢杂志

ObjectiveTo investigate the effect of rhPTH (1-34) and elcatonin on bone metabolism and serum secreted protein acidic and rich in cysteine ( SPARC ) in postmenopausal women with osteoporosis.Methods One hundred and twenty-four postmenopausal women with osteoporosis were randomly divided into 2 groups:One group was treated with recombinant human parathyroid hormone ( 1-34 ) [ rhPTH ( 1-34 ) ] 200 U/d by subcutaneous injection (PTH group,n =89 )and another group was treated with elcatonin 20 U/week by intramuscular injection (CT group,n =35 ) for 12 months.All patients received a basic therapy with oral calcium ( Ca 600 mg+ Vit D3125 U,q..d.).The bone mineral density ( BMD ) of lumbar spine( L2-4 ),the left femoral neck,greater trochanter,and Ward's triangle,serum calcium and phosphate were measured by baseline,6 months' and 12 months.Levels of serum bone-specific alkaline phosphatase( BSAP),serum secreted protein acidic and rich in cysteine (SPARC)were determined by an ELISA assay.ResultsBy 12 months,rhPTH ( 1-34 ) treatment significantly increased the lumbar spine L2-4 BMD 7.9％ (P＜0.05),serum calcium 8.3 ％ ( P＜ 0.05 ),serum BSAP 93.4％ ( P＜ 0.05 ),serum SPARC by 12.6％[ ( 195.68±59.57 vs 173.81 ±81.33 ) pμg/L,P＜0.05 ].Elcatonin therapy increased the lumbar spine L2-4 BMD by 3.2％ (P＜0.05) at the end of 12 months,but elcatonin did not influence serum calcium,BSAP and SPARC.The rhPTH( 1-34 ) increased lumbar spine L2-4 BMD more than elcatonin did at 12 months( P＜0.05 ).ConclusionrhPTH (1-34) could promote the bone anabolism more effectively than elcatonin did.Serum SPARC may play an important role in promoting osteogenesis by rhPTH.

Effects of secreted protein acidic and rich in cysteine peptide on change of ultramicrostructure and extracellular matrix secretion of human mesangial cells cultured in vitro / 第二军医大学学报

Objective: To investigate the effects of secreted protein acidic and rich in cysteine (SPARC) peptide on ultramicrostructure and extracellular matrix secretion of human mesangial cells cultured in vitro. Methods: Human mesangial cells (HMC) were incubated at the presence of SPARC peptide (50 μg/ml)for 48 h and 96 h separately; HMC cultured without SPARC peptide was taken as control. The cell ultramicrostructure was observed by transmission electron microscope. Real-time fluorescent quantitative PCR (RT-PCR) was used to detect mRNA levels of collagen type I (Col I), collagen type IV (Col IV), fibronectin (FN), and laminin (LN) 96 hours after culture, and the results were compared between the 2 groups. The secreted levels of Col I, Col IV, FN, and LN protein were measured and compared by enzyme-linked immunosorbent assay (ELISA) in the 2 groups. Results: There was no obvious change in HMC in the control group. After cultured for 48 hours, a few HMC in experimental group showed initial appearance of apoptosis; after cultured for 96 h, a great number of HMC had a typical apoptotic appearance and there were typical apoptotic bodies under electron microscope. RT-PCR showed that, compared with the control group, the experimental group had significantly decreased levels of Col I, Col IV and FN mRNA (P<0.05, P<0.0l); ELISA results showed that the secretions of Col I, ColIV, and FN protein in the experimental group were greatly lower than those in the control garoup (P<.05, P<0.01). Conclusion: SPARC peptide can effectively induce apoptosis of human mesangial cells and down regulate the secretion of extracellular matrix in vitro.

Concentrations of secreted protein acidic and rich in cysteine in serum and urine and its expression in kidney tissues of patients with IgA nephropathy / 第二军医大学学报

Objective: To investigate the concentrations of secreted protein acidic and rich in cysteine(SPARC) in the serum and urine of patients with IgA nephropathy and its expression in the kidney tissues. Methods: The concentrations of SPARC, tumor necrosis factor-a (TNF-a),interleukin 1β (IL-1β), and interleukin 6 (IL-6) in the serum and urine were measured with enzyme-linked immunosorbent assay(ELISA). The contents of SPARC protein in the culture medium of human mesangial cell (HMC) and human renal tubular epithelial cell (HKC), which had been treated with IL-6, were determined by ELISA. The expression and distribution of SPARC in IgA nephropathy and normal kidney tissues were observed by immunohistochemistry assay. Results: The concentrations of SPARC in serum and urine of IgA nephropathy patients were higher than those of the normal control subjects ([2.43±±1.22] μg/ml vs [0.69±0.21] 2μg/ml, [7.73±2.81] μg/ml vs [1.17±1.03]ρg/ml, P<0.01). The serum levels of TNF-α, IL-1β and IL-6 in IgA nephropathy group were significantly higher than those in the control group (P< 0.05); the urinary levels of TNF-α and IL-6 in IgA nephropathy group were also higher than those in the controls (P<0.01). SPARC protein secreted by HKC was higher than that by HMC (P<0.01). SPARC was weakly positive in normal distal cortical tubules. SPARC protein expression in tubular epithelial cells of IgA nephropathy patients was obviously higher than that of the normal controls. Conclusion: The secretion of SPARC by renal tubular epithelial cells is increased in patients with IgA nephropathy, which results in elevation of serum SPARC and may have a protective feedback inhibitory effect on HMC proliferation.

Effects of SPARC and its peptide on proliferation and apoptosis of human mesangial cells cultured in vitro / 中华肾脏病杂志

Objective To investigate the effects of SPARC (secreated protein acidic and rich in cysteine) and its peptide on proliferation, apoptosis and cell cycle of human mesangial cells cultured in vitro, and explore the possible mechanism. Methods Mesangial cells were incubated in the media with various concentrations of SPARC and its peptide cultured in vitro. Cell proliferation was assessed by MTT colorimetric assay. Cell cycle and apoptosis index were analyzed by flow cytometry. The expression of cyclinD1 and p21Wafl proteins in response to SPARC and its peptide in HMC was determined by Western blot. Results Various concentrations of SPARC and its peptide could significantly inhibit the proliferation of mesangial cells in dose- and time-dependent manner, regulate the cell cycle at phrase G-0/G1 increased while cells phrase S reduced, and could also induce apoptosis. Under the stimulation of SPARC and its peptide, the expression of cyclinDl in HMC decreased markedly meanwhile the expression of p21Wafl increased significantly. Conclusions SPARC and its peptide can effectively inhibit HMC proliferation and regulate cell cycle progression. The mechanism may be mediated by inhibiting cyclinDl and stimulating p21Wafl expression, subsequently blocking cells passing through G-S check point, which will be useful for treating mesangial proliferative glomerulonephritis.

Concentrations of secreted protein acidic and rich in cysteine in serum and urine and its expression in kidney tissues of patients with IgA nephropathy / 第二军医大学学报

Objective:To investigate the concentrations of secreted protein acidic and rich in cysteine(SPARC)in the serum and urine of patients with IgA nephropathy and its expression in the kidney tissues.Methods:The concentrations of SPARC, tumor necrosis factor-?(TNF-?),interleukin 1?(IL-1?),and interleukin 6(IL-6)in the serum and urine were measured with enzyme-linked immunosorbent assay(ELISA).The contents of'SPARC protein in the culture medium of human mesangial cell (HMC)and human renal tubular epithelial cell(HKC),which had been treated with IL-6,were determined by ELISA.The ex- pression and distribution of SPARC in IgA nephropathy and normal kidney tissues were observed by immunohistochemistry as- say.Results:The concentrations of SPARC in serum and urine of IgA nephropathy patients were higher than those of the normal control subjects([2.43?1.22]?g/ml vs[0.69?0.21]?g/ml,[7.73?2.81]?g/ml vs[1.17?1.03]?g/ml,P