Abstract / Summary
Renal fibrosis plays a central role in the progression of chronic kidney disease (CKD). Previous studies have reported that the bile acid receptors farnesoid X receptor (FXR) and Takeda G protein–coupled receptor 5 (TGR5) can protect against fibrosis development. However, these studies primarily relied on animal models or cell monocultures. In animal models, systemic influences can obscure kidney-specific effects, whereas cell monocultures lack the complex multicellular interactions that characterize kidney fibrosis. Here, we investigated whether the antifibrotic effects of FXR and TGR5 activation are also present in a multicellular tissue-based fibrosis model, namely mouse precision-cut kidney slices (mPCKS). Our results demonstrated that several bile acid receptors, including FXR and TGR5, are expressed in mPCKS. In addition, treatment with the endogenous FXR agonist chenodeoxycholic acid (CDCA) effectively attenuated both culture- and TGF-β-induced fibrosis, which was associated with reduced SMAD2/3 protein levels. Notably, this effect appeared to be independent of FXR and TGR5 signaling. In contrast, lithocholic acid induced apoptosis in mPCKS. However, it is uncertain whether this is mediated through TGR5. Together, our findings demonstrate that mPCKS can be used to study bile acid signaling in renal fibrosis and that CDCA directly attenuates fibrosis in kidney tissue.