Tauroursodeoxycholic acid attenuates cyclosporine-induced renal fibrogenesis in the mouse model

Biochim Biophys Acta Gen Subj. 2019 Jul;1863(7):1210-1216. doi: 10.1016/j.bbagen.2019.04.016. Epub 2019 Apr 24.


Chronic exposure to cyclosporine causes nephrotoxicity and organ damage. Here we show that cyclosporine nephrotoxicity in vivo is associated with the activation of the unfolded protein response (UPR) pathway to initiate tissue fibrosis. We demonstrate that cyclosporine therapy activated the IRE1α branch of the unfolded protein response (UPR) and stimulated the TGFβ1 signaling pathway in the kidneys of male mice. Co-administration of the proteostasis promoter tauroursodeoxycholic acid (TUDCA) with cyclosporine inhibited the UPR pathway in the kidneys of treated male mice as well as decreased the development of renal fibrogenesis.

Keywords: Cyclosporine; Fibrogenesis; Kidney disease; Proteostasis promoter; TUDCA; Unfolded protein responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclosporine / pharmacology*
  • Disease Models, Animal
  • Fibrosis / chemically induced*
  • Kidney / drug effects*
  • Kidney / pathology
  • Kidney Diseases / prevention & control*
  • Male
  • Mice
  • Taurochenodeoxycholic Acid / pharmacology*
  • Unfolded Protein Response


  • Taurochenodeoxycholic Acid
  • ursodoxicoltaurine
  • Cyclosporine