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Objective To investigate the effect of all-trans retinoic acid (ATRA) on transforming growth factor β1 (TGF-β1)/Notch signaling pathway in injured podocytes induced by adriamycin (ADR) in vitro.Methods Podocytes cultured in vitro were randomly divided into normal group,model group,ATRA treatment control group,12-hour ATRA intervention group and 24-hour ATRA intervention group.Morphological changes were observed by using light microscope.The expressions of TGF-β1,podocin,Notch 1,Jagged 1 mRNA were evaluated through real-time polymerase chain reaction (RT-PCR) and the corresponding proteins were detected by using Western blot.Results (1) No obvious changes between normal group and ATRA treatment control group were revealed as the plump podocytes and distinct outline were found in light microscope,while podocytes in model group showed disordered arrangement,fuzzy boundary,atrophy,hypertrophy and increased cellular debris.Of note,the podocytes in 12-hour ATRA intervention group and 24-hour ATRA intervention group almost returned to normal.(2) In contrast with those in model group,the amounts of TGF-β1,Notchl,Jaggedl mRNA levels decreased in 12-hour ATRA intervention group (1.34 ±0.43 vs.4.16 ±0.31,1.67 ±0.2 vs.4.21 ±0.92,2.08 ±0.27 vs.5.14 ±0.63,q =23.83,11.45,19.67,all P ＜0.05) and 24-hour ATRA intervention group (1.22 ± 0.16 vs.4.16 ± 0.31,1.73 ± 0.53 vs.4.21 ± 0.92,2.08 ± 0.29 vs.5.14 ± 0.63,q =24.85,11.18,19.67,all P ＜ 0.05),and the differences were significant;similar trend was detected in the protein levels (1.04 ± 0.03 vs.4.31 ± 0.10,1.06 ± 0.04 vs.4.47 ± 0.24,1.07 ± 0.04 vs.4.20 ± 0.16,1.06 ±0.03 vs.4.31 ±0.10,1.07 ±0.03 vs.4.47 ±0.24,1.09 ±0.03 vs.4.20 ±0.16,q =163.50,69.61,90.36,162.50,69.40,89.78,all P ＜ 0.05),and the differences were significant;whereas the level of podocin mRNA (1.13 ±0.05 vs.0.40 ± 0.06,1.16 ± 0.03 vs.0.40 ± 0.06,q =36.50,38.00,all P ＜ 0.05) and protein (1.01 ± 0.01 vs.0.44 ±0.01,1.02 ±0.01 vs.0.44 ±0.01,q =180.25,183.41,all P ＜0.05) increased,and the differences were sig nificant.(3) The expressions of Notch1,Jagged1 mRNA were positively correlated with TGF-β1 mRNA (r =0.84,1.00,all P ＜ 0.05),but negatively correlated with podocin mRNA (r =-0.95,-0.94,all P ＜ 0.05) in model group.Conclusions ATRA might alleviate podocyte injury through cutting the expressions of TGF-β1,Notch1,Jagged1 and raising the expression of podocin in injured podocytes induced by ADR.
ABSTRACT
Retinoic acid (RA) receptor, is a group of ligand-regulated nuclear transcription factors and widely distributed in various tissue cells. The different subtypes of RA receptor can polymerize into homologous or heterogenous dimmers, and then participate in the physiological and pathological processes of embryonic development, cell proliferation and differentiation, and apoptosis. However, the relationship between the expression of RA receptor and the diseases is different in diverse cells or tissues. Recent researches demonstrated that RA receptor is closely related to the pathogenesis and development of renal diseases. This article aims to review the role of the RA receptor and its signal pathway in the development of renal diseases.
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Objective To detect and investigate the expression and the effect of Prohibitin (PHB) in rats with renal interstitial fibrosis (RIF) induced by unilateral ureteral obstruction (UUO) .Methods Forty-eight Wistar male rats (6-weeks-old) were randomly assigned into 2 groups,sham-operated and model group.The model group rats were subjected to left ureteral ligation after anesthesia and the sham-operated group rats were subjected to sham operation.Six rats were killed 7,14,21,28 days after operation respectively.The renal tissues were collected.The index of RIF was calculated.The expressions of mRNA and protein of PHB were assayed by real time polymerase chain reaction and immunohistochemistry. Results Compared with sham-operation group,at each time point,the model group had significantly increased index of RIF (P < 0.01) and the obstruction for a longer period showed the higher index; the model group had significantly decreased expression of mRNA and protein of PHB (P < 0.01) and the obstruction for a longer period showed the lower expression; the model group had significantly increased expression of mRNA and protein of TGF-β1 (P < 0.01) and the obstruction for a longer period showed the higher expression.Correlation analysis showed that the index of RIF was negatively correlated with FHB (γ = -0.825) and positively correlated with TGF-β1 (γ = 0.995),while there was a positive correlation between PHB and TGF-β1 (γ = -0.786).Conclusions The lower expression of PHB in renal tissue of UUO rats might suggest that it play an important role in RIF.
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Aim To investigate the effects of all-trans retinoic acid and benazepril on the expression of ?-smooth muscle actin in rats with glomerulosclerosis.Methods 80 Wistar male Rats were randomly assigned into the following groups: control group,model group,ATRA treatment group and benazepril treatment group,20 rats in each group.GS rats were uninephrectomized and injected with adriamycin(5mg?kg-1) after one week through the tail vein.All rats were sacrificed at the 12th week,GS was evaluated by glomerulosclerosis index(GSI) system.The expression of ?-SMA was assessed by reverse transcription-polymerase chain reaction(RT-PCR) and immunohistochemistry.Results Comparing with control group,the expression of ?-SMA mRNA and protein were decreased significantly in ATRA treatment group and benazepril treatment group(P0.05).Conclusions The postponed effects of ATRA and benazepril on GS were evident and equivalent.