Retinoic acid improves nephrotoxic serum–induced glomerulonephritis through activation of podocyte retinoic acid receptor α
| Autor: | Yan Dai, Xiaoqiang Ding, Weijing Cai, Marcus J. Moeller, Stuart J. Shankland, Shuchita Sharma, Norbert B. Ghyselinck, Jeffrey Pippin, Ruijie Liu, Kyung Lee, John Cijiang He, Anqun Chen, Leyi Gu, David J. Salant, Fadi Salem, Peter Y. Chuang |
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| Přispěvatelé: | Institut de Chimie de Clermont-Ferrand (ICCF), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Biopsy [SDV]Life Sciences [q-bio] 030232 urology & nephrology Retinoic acid Tretinoin Biology Protective Agents Article Podocyte 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Glomerulonephritis Internal medicine medicine Animals Humans Receptor Cells Cultured Autoantibodies Cell Proliferation Mice Knockout Podocytes Retinoic Acid Receptor alpha Transdifferentiation Intracellular Signaling Peptides and Proteins Membrane Proteins Bowman Capsule medicine.disease Mice Inbred C57BL Retinoic acid receptor 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry Nephrology Retinoic acid receptor alpha Knockout mouse Cell Transdifferentiation Cancer research Biomarkers |
| Zdroj: | Kidney International Kidney International, Nature Publishing Group, 2017, 92 (6), pp.1444-1457. ⟨10.1016/j.kint.2017.04.026⟩ Kidney International, 2017, 92 (6), pp.1444-1457. ⟨10.1016/j.kint.2017.04.026⟩ |
| ISSN: | 0085-2538 1523-1755 |
| Popis: | Proliferation of glomerular epithelial cells, including podocytes, is a key histologic feature of crescentic glomerulonephritis. We previously found that retinoic acid (RA) inhibits proliferation and induces differentiation of podocytes by activating RA receptor-α (RARα) in a murine model of HIV-associated nephropathy. Here, we examined whether RA would similarly protect podocytes against nephrotoxic serum–induced crescentic glomerulonephritis and whether this effect was mediated by podocyte RARα. RA treatment markedly improved renal function and reduced the number of crescentic lesions in nephritic wild-type mice, while this protection was largely lost in mice with podocyte-specific ablation of Rara (Pod-Rara knockout). At a cellular level, RA significantly restored the expression of podocyte differentiation markers in nephritic wild-type mice, but not in nephritic Pod-Rara knockout mice. Furthermore, RA suppressed the expression of cell injury, proliferation, and parietal epithelial cell markers in nephritic wild-type mice, all of which were significantly dampened in nephritic Pod-Rara knockout mice. Interestingly, RA treatment led to the coexpression of podocyte and parietal epithelial cell markers in a small subset of glomerular cells in nephritic mice, suggesting that RA may induce transdifferentiation of parietal epithelial cells toward a podocyte phenotype. In vitro , RA directly inhibited the proliferation of parietal epithelial cells and enhanced the expression of podocyte markers. In vivo lineage tracing of labeled parietal epithelial cells confirmed that RA increased the number of parietal epithelial cells expressing podocyte markers in nephritic glomeruli. Thus, RA attenuates crescentic glomerulonephritis primarily through RARα-mediated protection of podocytes and in part through the inhibition of parietal epithelial cell proliferation and induction of their transdifferentiation into podocytes. |
| Databáze: | OpenAIRE |
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