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