• DOI:10.1152/ajprenal.00230.2019
• Corpus ID: 202747048

BMP1 inhibitor UK-383,367 attenuates renal fibrosis and inflammation in CKD.

@article{Bai2019BMP1IU,
  title={BMP1 inhibitor UK-383,367 attenuates renal fibrosis and inflammation in CKD.},
  author={Mi Bai and Juan Lei and Shuqin Wang and Dan Ding and Xiaowen Yu and Yan Guo and Shuang Chen and Yang Du and de Oliveira Li and Yue Zhang and Songming Huang and Zhanjun Jia and Aihua Zhang},
  journal={American journal of physiology. Renal physiology},
  year={2019}
}

• M. Bai, Juan Lei, +10 authors A. Zhang
• Published 1 December 2019
• Medicine, Biology, Chemistry
• American journal of physiology. Renal physiology

Renal fibrosis is a key pathological phenomenon of chronic kidney disease (CKD), contributing to the progressive loss of renal function. UK383,367 is a procollagen C-proteinase inhibitor that has been selected as a candidate for dermal anti-scarring agent, while its role in renal fibrosis is unclear. In this study, UK383,367 was applied to a CKD mouse model of unilateral ureteral obstruction (UUO) and cell lines of renal tubular epithelial cells (mPTCs) and renal fibroblast cells (NRK-49F) challenged by TGF-β1. In vivo, bone morphogenetic protein 1 (BMP1), the target of UK383,367, was significantly enhanced in UUO mouse kidneys and CKD patients' renal biopsies. Strikingly, UK383,367 administration ameliorates tubulointerstitial fibrosis shown by Masson's trichrome staining in line with the blocked expression of collagen I/III, fibronectin, and α-SMA in the kidneys from UUO mice. Similarly, the enhanced inflammatory factors in obstructive kidneys were also blunted. In vitro, UK383,367 pretreatment inhibited the induction of collagen I/III, fibronectin, and α-SMA in both mPTCs and NRK-49F cells treated with TGF-β1. Taken together, these findings indicated that BMP1 inhibitor UK383,367 could serve as a potential drug in antagonizing CKD renal fibrosis by acting on the maturation and deposition of collagen and subsequent profibrotic response and inflammation.