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RIG-I aggravates interstitial fibrosis via c-Myc-mediated fibroblast activation in UUO mice.
- Source :
-
Journal of Molecular Medicine . Apr2020, Vol. 98 Issue 4, p527-540. 14p. - Publication Year :
- 2020
-
Abstract
- Progressive tubulointerstitial fibrosis is the common final outcome for all kidney diseases evolving into chronic kidney disease (CKD), whereas molecular mechanisms driving fibrogenesis remain elusive. Retinoic acid-inducible gene-I (RIG-I), an intracellular pattern recognition receptor, is originally identified participating in immune response by recognizing virus RNA. Here, we revealed for the first time that RIG-I was induced in unilateral ureteral obstruction (UUO) and folic acid (FA) renal fibrosis models and moderate-degree renal fibrosis patients. Besides, we found RIG-I was mainly located in renal tubular epithelial cells and promoted the production and release of inflammatory cytokines, such as interleukin (IL)-1β and IL-6 through activation of NF-κB. Inflammatory cytokines released by tubular epithelial cells activated c-Myc-mediated TGF-β/Smad signaling in fibroblasts, which in turn aggravated interstitial fibrosis by promoting fibroblast activation and production of extracellular matrix components (ECM). Deficiency of RIG-I attenuated renal fibrosis by the regulation of inflammatory responses, c-Myc expression, and fibroblast activation. Besides, gene silencing of RIG-I reduced inflammatory cytokines in cultured tubular epithelial cells treated with Angiotensin II. Knockdown of c-Myc or c-Myc inhibitor blocked IL-1β-induced fibroblast activation. Collectively, our study demonstrates that RIG-I plays a significant role in the progress of renal fibrosis via regulating c-Myc-mediated fibroblast activation. Key messages: • RIG-I was constantly elevated in kidneys from renal fibrotic mice. • RIG-I facilitated inflammatory cytokine production in tubular epithelial cells. • RIG-I aggravated renal fibrosis via c-Myc-mediated TGF-β/Smad activation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09462716
- Volume :
- 98
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Journal of Molecular Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 143039467
- Full Text :
- https://doi.org/10.1007/s00109-020-01879-x