Long non-coding RNA lnc-CHAF1B-3 promotes renal interstitial fibrosis by regulating EMT-related genes in renal proximal tubular cells

• Published in: Molecular therapy. Nucleic acids Vol. 31; pp. 139 - 150
• Main Authors: Imai, Kentaro, Ishimoto, Takuji, Doke, Tomohito, Tsuboi, Toshiki, Watanabe, Yu, Katsushima, Keisuke, Suzuki, Miho, Oishi, Hideto, Furuhashi, Kazuhiro, Ito, Yasuhiko, Kondo, Yutaka, Maruyama, Shoichi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.03.2023; American Society of Gene & Cell Therapy; Elsevier
• Subjects: epithelial-to-mesenchymal transition; IgA nephropathy; lnc-CHAF1B-3; long non-coding RNA; MT: Non-coding RNAs; Original; proximal tubular cell; renal interstitial fibrosis; IgA nephropathy; proximal tubular cell; long non-coding RNA; MT: Non-coding RNAs; lnc-CHAF1B-3; renal interstitial fibrosis; epithelial-to-mesenchymal transition
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2022.12.011

Renal interstitial fibrosis (RIF) is a common pathological manifestation of chronic kidney diseases. Epithelial-mesenchymal transition (EMT) of tubular epithelial cells is considered a major cause of RIF. Although long non-coding RNAs (lncRNAs) are reportedly involved in various pathophysiological processes, the roles and underlying molecular mechanisms of lncRNAs in the progression of RIF are poorly understood. In this study, we investigated the function of lncRNAs in RIF. Microarray assays showed that expression of the lncRNA lnc-CHAF1B-3 (also called claudin 14 antisense RNA 1) was significantly upregulated in human renal proximal tubular cells by both transforming growth factor-β1 (TGF-β1) and hypoxic stimulation, accompanied with increased expression of EMT-related genes. Knockdown of lnc-CHAF1B-3 significantly suppressed TGF-β1-induced upregulated expression of collagen type I alpha 1, cadherin-2, plasminogen activator inhibitor-1, snail family transcriptional repressor I (SNAI1) and SNAI2. Quantitative reverse transcriptase PCR analyses of paraffin-embedded kidney biopsy samples from IgA nephropathy patients revealed lnc-CHAF1B-3 expression was correlated positively with urinary protein levels and correlated negatively with estimated glomerular filtration rate. In situ hybridization demonstrated that lnc-CHAF1B-3 is expressed only in proximal tubules. These findings suggest lnc-CHAF1B-3 affects the progression of RIF by regulating EMT-related signaling. Thus, lnc-CHAF1B-3 is a potential target in the treatment of RIF. [Display omitted] Imai et al. found that a lncRNA, lnc-CHAF1B-3, regulates EMT-related signaling in human renal proximal tubules, and that renal lnc-CHAF1B-3 expression is associated with disease severity of IgA nephropathy, including interstitial fibrosis. Thus, lnc-CHAF1B-3 may serve as a potential target for the treatment of renal fibrosis.