Effect of all-trans retinoic acid on transforming growth factor-β1/Notch signaling pathway in injured podocytes induced by Adriamycin / 中华实用儿科临床杂志

ABSTRACT

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.