Retinoic acid regulation of mesangial cell apoptosis.
Retinoic acid (RA) is recently used for the treatment of experimental glomerular diseases. However, mechanisms underlying its therapeutic effects are largely unknown. We recently reported that RA has the potential for protecting certain cells from particular injury. A typical example is its effect on oxidant-induced apoptosis of mesangial cells. Mesangial cells exposed to hydrogen peroxide undergo apoptosis through activation of the c-Jun N-terminal kinase activator protein 1 pathway. RA dramatically inhibits this process via suppression of c-fos/c-jun expression and inhibition of the c-Jun N-terminal kinase activation. The anti-apoptotic effect of RA is mediated by both nuclear receptor dependent and nuclear receptor independent mechanisms and is, at least in part, mediated by induction of mitogen-activated protein kinase phosphatase 1. In this review, we briefly summarize the current knowledge on molecular mechanisms involved in the anti-apoptotic effects of RA.
Xu
Qihe
Q
Department of Medicine, Royal Free and University College Medical School, University College London, UK.
Konta
Tsuneo
T
Kitamura
Masanori
M
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D018797:Cell Cycle Proteins; D054638:Dual Specificity Phosphatase 1; D005786:Gene Expression Regulation; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects; D017874:Immediate-Early Proteins / Q000378:metabolism; D008957:Models, Genetic; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D047488:Retinoid X Receptors; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D014212:Tretinoin; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; D017027:Protein Tyrosine Phosphatases