The role of retinoic acid receptors in the signal pathway of all-trans retinoic acid-induced differentiation in adriamycin-induced podocyte injury.
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.
Department of Pediatrics, The First Affiliated Hospital of GuangXi Medical University , Nanning , China .
Xiu-Ping
XP
Chen
Feng-Ying
FY
Lei
Yuan-Han
YH
Qin
Tian-Biao
TB
Zhou
Ling
L
Jiang
Yan-Jun
YJ
Zhao
Wei-Fang
WF
Huang
Qi-Liu
QL
Peng
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D004317:Doxorubicin / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D050199:Podocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology*
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D018168:Receptors, Retinoic Acid; C113267:nephrin; D014212:Tretinoin; D004317:Doxorubicin
All-trans retinoic acid; differentiation; injured podocytes; retinoic acid receptors