eprintid: 10090356 rev_number: 17 eprint_status: archive userid: 608 dir: disk0/10/09/03/56 datestamp: 2020-01-27 13:03:50 lastmod: 2021-11-10 23:08:02 status_changed: 2020-01-27 13:03:50 type: article metadata_visibility: show creators_name: Chen, X creators_name: Wu, Y creators_name: Diao, Z creators_name: Han, X creators_name: Li, D creators_name: Ruan, X creators_name: Liu, W title: C1q/tumor necrosis factor‐related protein‐3 improves renal fibrosis via inhibiting notch signaling pathways ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: G93 keywords: C1q/tumor necrosis factor-related protein-3 (CTRP3), Notch signaling pathway, TGF-β1, renal interstitial fibrosis, tubular epithelial cells note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. abstract: C1q/tumor necrosis factor-related protein-3 (CTRP3) has been extensively reported as an important role involved in antifibrosis, antiapoptosis, and anti-inflammation. However, the role of CTRP3 involved in renal fibrosis remains unclear. Our current study explored the role of CTRP3 in renal fibrosis and its underlying mechanisms by using serums and renal biopsy specimens from renal fibrosis patients and control subjects, rats models with the surgery of unilateral ureteral obstruction (UUO) and human renal proximal tubular epithelial cells (HRPTEpiCs). We found that circulating levels of CTRP3 had no significant difference between renal fibrosis patients and healthy subjects; however, renal CTRP3 expression was markedly downregulated in the fibrotic region with an abundant expression of collagen-I. In UUO rat models, circulating levels of CTRP3 have not changed with the prolonged obstruction of the kidney; renal CTRP3 expression was decreased with the severity of renal fibrosis; adenovirus-mediated CTRP3 treatment inhibited renal interstitial fibrosis. In vitro experiments revealed that CTRP3 attenuates TGF-β1 induced tubular epithelial cells fibrotic changes; CTRP3 knockdown facilitates the expression of fibrotic markers in TGF-β1-induced HRPTEpiCs; recombinant CTRP3 or adenovirus-mediated CTRP3 overexpression significantly inhibited the Notch signaling pathway-associated factors, and knockdown of CTRP3 increased TGF-β1-mediated activation of the Notch signaling pathways. Collectively, our current study found that CTRP3 could improve renal fibrosis, to some extent, through inhibiting the Notch pathway. date: 2019-12 date_type: published official_url: https://doi.org/10.1002/jcp.28801 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1656634 doi: 10.1002/jcp.28801 lyricists_name: Ruan, Xiong-Zhong lyricists_id: XZRUA13 actors_name: Ruan, Xiong-Zhong actors_id: XZRUA13 actors_role: owner full_text_status: public publication: Journal of Cellular Physiology volume: 234 number: 12 pagerange: 22352-22364 event_location: United States issn: 1097-4652 citation: Chen, X; Wu, Y; Diao, Z; Han, X; Li, D; Ruan, X; Liu, W; (2019) C1q/tumor necrosis factor‐related protein‐3 improves renal fibrosis via inhibiting notch signaling pathways. Journal of Cellular Physiology , 234 (12) pp. 22352-22364. 10.1002/jcp.28801 <https://doi.org/10.1002/jcp.28801>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10090356/1/Xinpan%20Chen%20.pdf