The role of retinoic acid receptors in the signal pathway of all-trans retinoic acid-induced differentiation in adriamycin-induced podocyte injury

Abstract

All-trans retinoic acid (ATRA) plays an essential role in cell survival and differentiation by binding to retinoic acid receptors (RARs), including RAR-α, RAR-β, and RAR-γ. Injury to podocytes is the most frequent cause of glomerulosclerosis (GS). This study was performed to investigate which of the RAR subtypes is involved in the signal pathway of ATRA-induced differentiation of injured podocytes. ATRA (0.1 μM) was administered to Adriamycin (ADR)-induced, injured podocytes, in vitro. Morphological changes were observed. The protein/mRNA expression of podocin, nephrin, transforming growth factor β1(TGF-β1), and the RARs (RAR-α,β,γ) was measured by RT-PCR and Western blotting. ATRA treatment ameliorated cell hypertrophy and reduced the shedding of the cytoplasm which was observed under light microscope and the extension of the foot processes was observed under scan electron microscope. Compared with the injured podocytes, ATRA exposure significantly increased the protein/mRNA expression of nephrin and podocin and it markedly reduced TGF-β1 (all p < 0.05). Compared with the injured podocytes, the protein/mRNA expression of RAR-α and RAR-γ was significantly increased after ATRA exposure; however, the expression level of RAR-β was not significantly different. The RAR-α/γ protein expression level was positively correlated with nephrin and podocin (−α, r = 0.637, 0.663; −γ, r = 0.882, 0.878; all p < 0.05), and negatively correlated with TGF-β1 (−α, r = −0.650; −γ, r = −0.739; all p < 0.05). The RAR-β protein expression level was not correlated with nephrin, podocin and TGF-β1 (r = −0.312, 0.079, −0.279; all p > 0.05). In conclusion, RAR-α/γ (and RAR-β to a lesser degree) may be involved in the signal pathway of ATRA-induced differentiation in injured podocytes.

• All-trans retinoic acid
• differentiation
• injured podocytes
• retinoic acid receptors

Acknowledgements

The authors would like to gratefully acknowledge the most helpful comments on this paper received from Professor Liang Rong, Department of Pediatric-Neonatology, Baylor College of Medicine, Houston, TX.