Sanglifehrin A mitigates multi-organ fibrosis by targeting the collagen chaperone cyclophilin B

Pathological deposition and crosslinking of collagen type I by activated myofibroblasts drives progressive tissue fibrosis. Therapies that inhibit collagen synthesis have potential as anti-fibrotic agents. We identify the collagen chaperone cyclophilin B as a major cellular target of the natural product sanglifehrin A (SfA) using photo-affinity labeling and chemical proteomics. Mechanistically, SfA inhibits and induces the secretion of cyclophilin B from the endoplasmic reticulum (ER) and prevents TGF-

  • Flaxman, H. A.
  • Chrysovergi, M. A.
  • Han, H.
  • Kabir, F.
  • Lister, R. T.
  • Chang, C. F.
  • Yvon, R.
  • Black, K. E.
  • Weigert, A.
  • Savai, R.
  • Egea-Zorrilla, A.
  • Pardo-Saganta, A.
  • Lagares, D.
  • Woo, C. M.

Keywords

  • Collagens
  • Drug therapy
  • Fibrosis
  • Inflammation
  • Therapeutics
Publication details
DOI: 10.1172/jci.insight.171162
Journal: JCI Insight
Work Type: Original
Access number: 38900587
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