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DsbA-L mediated renal tubulointerstitial fibrosis in UUO mice

Author

Listed:
  • Xiaozhou Li

    (Central South University
    Central South University)

  • Jian Pan

    (Central South University
    Central South University)

  • Huiling Li

    (Central South University)

  • Guangdi Li

    (Central South University)

  • Xiangfeng Liu

    (Central South University)

  • Bohao Liu

    (Central South University
    Central South University)

  • Zhibiao He

    (Central South University
    Central South University)

  • Zhengyu Peng

    (Central South University
    Central South University)

  • Hongliang Zhang

    (Central South University
    Central South University)

  • Yijian Li

    (Central South University)

  • Xudong Xiang

    (Central South University
    Central South University)

  • Xiangping Chai

    (Central South University
    Central South University)

  • Yunchang Yuan

    (Central South University)

  • Peilin Zheng

    (The First Affiliated Hospital of Southern University of Science and Technology)

  • Feng Liu

    (Central South University
    University of Texas Health at San Antonio)

  • Dongshan Zhang

    (Central South University
    Central South University)

Abstract

Recent studies have reported that upregulation of disulfide-bond A oxidoreductase-like protein (DsbA-L) prevented lipid-induced renal injury in diabetic nephropathy (DN). However, the role and regulation of proximal tubular DsbA-L for renal tubulointerstitial fibrosis (TIF) remains unclear. In current study, we found that a proximal tubules-specific DsbA-L knockout mouse (PT-DsbA-L-KO) attenuated UUO-induced TIF, renal cell apoptosis and inflammation. Mechanistically, the DsbA-L interacted with Hsp90 in mitochondria of BUMPT cells which activated the signaling of Smad3 and p53 to produce connective tissue growth factor (CTGF) and then resulted in accumulation of ECM of BUMPT cells and mouse kidney fibroblasts. In addition, the progression of TIF caused by UUO, ischemic/reperfusion (I/R), aristolochic acid, and repeated acute low-dose cisplatin was also alleviated in PT-DsbA-L-KO mice via the activation of Hsp90 /Smad3 and p53/CTGF axis. Finally, the above molecular changes were verified in the kidney biopsies from patients with obstructive nephropathy (Ob). Together, these results suggest that DsbA-L in proximal tubular cells promotes TIF via activation of the Hsp90 /Smad3 and p53/CTGF axis.

Suggested Citation

  • Xiaozhou Li & Jian Pan & Huiling Li & Guangdi Li & Xiangfeng Liu & Bohao Liu & Zhibiao He & Zhengyu Peng & Hongliang Zhang & Yijian Li & Xudong Xiang & Xiangping Chai & Yunchang Yuan & Peilin Zheng & , 2020. "DsbA-L mediated renal tubulointerstitial fibrosis in UUO mice," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18304-z
    DOI: 10.1038/s41467-020-18304-z
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