TGF-β-SMAD3 signaling mediates hepatic bile acid and phospholipid metabolism following lithocholic acid-induced liver injury

A model of in vitro UDP-glucuronosyltransferase inhibition by bile acids predicts possible metabolic disorders

“…The detailed metabolic inhibition profi le of BAs toward important UGT isoforms was clarifi ed in the present study, and TLCA was demonstrated to be the strongest inhibitor toward most of UGT isoforms, followed by LCA, which is consistent with the reports in which LCA and TLCA were reported to be able to signifi cantly induce the liver damage ( 29,30 ). LCA can be metabolized through UGT isoform-catalyzed glucuronidation elimination, so, the wide inhibition of LCA toward UGT isoforms was observed in the present study.…”

Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression

“…Thus, elucidation of the function of bile acid metabolites in the intestine could facilitate our understanding of the mechanisms associated with toxicity and disease states. For example, lithocholic acid (LCA)-induced hepatotoxicity can disrupt the bile acids homeostasis, and therapeutic targets were found based on the alteration of bile acids, including the TGF-β-SMAD3 signaling pathway (Matsubara et al , 2012) and intestinal cytochrome CYP3A4 (Cheng et al , 2014). The present study demonstrated CPT-11 induced disruption of the bile acids cycle, including altered levels of DCA and TDCA, the most significantly changed bile acids in liver, bile and ileum.…”

Tumor Necrosis Factor and Transforming Growth Factor β Regulate Clock Genes by Controlling the Expression of the Cold Inducible RNA-binding Protein (CIRBP)

“…TGF␤ modulates key aspects of metabolic processes such as hepatic phospholipid and bile homeostasis. Both the organic solute transporter OST␤ and CYP7A1, the ratelimiting enzyme of bile acid synthesis, are regulated by TGF␤ (46). Moreover, TGF␤ is involved in energy metabolism and energy-sensing pathways (47,48).…”