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The yin and yang of retinoic acid signaling in kidney diseases
Qingqing Wei, Zheng Dong
Qingqing Wei, Zheng Dong
Published September 14, 2020
Citation Information: J Clin Invest. 2020;130(10):5124-5126. https://doi.org/10.1172/JCI141712.
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The yin and yang of retinoic acid signaling in kidney diseases

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Abstract

Retinoic acid (RA) signaling is involved in various physiological and pathological conditions, including development, tumorigenesis, inflammation, and tissue damage and repair. In kidneys, the beneficial effect of RA has been reported in multiple disease models, such as glomerulosclerosis, renal fibrosis, and acute kidney injury. In this issue of the JCI, Chen et al. report a pathway activated by RA signaling that is mediated by the retinoic acid receptor responder protein 1 (RARRES1). Specifically, RARRES1, which is proteolytically cleaved to release the extracellular domain, was endocytosed by podocytes to induce apoptosis and glomerular dysfunction kidney disease. These findings unveil the contrasting aspects, a Janus face, of RA signaling that may guide its therapeutic use.

Authors

Qingqing Wei, Zheng Dong

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Figure 1

The yin and yang of RA signaling in podocyte injury and protection.

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The yin and yang of RA signaling in podocyte injury and protection.
RA b...
RA binds to and activates nuclear receptors RAR/RXR, resulting in expression changes in protective or injurious genes. RARRES1, a gene induced by RA signaling, is cleaved by MMPs to release its C-terminal fragment, which is then endocytosed to activate the RIOK1/p53 apoptosis pathway in podocytes.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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