Ursodesoxycholic acid alleviates liver fibrosis via proregeneration by activation of the ID1‐WNT2/HGF signaling pathway

Abstract

Background The human liver possesses a remarkable capacity for self‐repair. However, liver fibrosis remains a serious medical concern, potentially progressing to end‐stage liver cirrhosis and even death. Liver fibrosis is characterized by excess accumulation of extracellular matrix in response to chronic injury. Liver regenerative ability, a strong indicator of liver health, is important in resisting fibrosis. In this study, we provide evidence that ursodesoxycholic acid (UDCA) can alleviate liver fibrosis by promoting liver regeneration via activation of the ID1‐WNT2/hepatocyte growth factor (HGF) pathway. Methods Bile duct ligation (BDL) and partial hepatectomy (PH) mouse models were used to verify the effects of UDCA on liver fibrosis, regeneration, and the ID1‐WNT2/HGF pathway. An Id1 knockdown mouse model was also used to assess the role of Id1 in UDCA alleviation of liver fibrosis. Results Our results demonstrate that UDCA can alleviate liver fibrosis in the BDL mice and promote liver regeneration via the ID1‐WNT2/HGF pathway in PH mice. In addition, Id1 knockdown abolished the protection afforded by UDCA in BDL mice. Conclusions We conclude that UDCA protects against liver fibrosis by proregeneration via activation of the ID1‐WNT2/HGF pathway.

Wogonoside attenuates liver fibrosis by triggering hepatic stellate cell ferroptosis through SOCS1/P53/SLC7A11 pathway

“…In pharmacodynamic experiments, a positive control medicine is practiced to evaluate whether therapeutic effect of the target drug is exceeded to that of the clinical medicine. Nevertheless, a positive control group is not necessary for every trial (Dong et al, 2021; Jiang et al, 2020; Leng et al, 2018). In general, if the results of drug experiments are ineffective, a positive control group is needed.…”

MiR-203 is an anti-obese microRNA by targeting apical sodium-dependent bile acid transporter

“…For secondary bile acid, miR-203 overexpression remarkably decreased TωMCA (tauro-ω-muricholic); but increased TUDCA (tauroursodeoxycholic acid), TDCA (taurodeoxycholic acid), and DCA (deoxycholic acid) ( Figures S4 E–S4H). Studies have revealed that TβMCA ( Oteng et al., 2021 ), TCA ( Azzimato et al., 2021 ), TCDCA ( Zhang et al., 2021a ), and TωMCA ( Nie et al., 2012 )were significantly increased in obesity; while the downregulated UDCA ( Dong et al., 2021 ), TUDCA ( Zhang et al., 2021b ), TDCA ( Lei et al., 2017 ) and DCA ( Yoshimoto et al., 2013 ) were harmful to liver or lipid metabolism. These parameters were corrected in miR-203 overexpression mice.…”

“…The primary BAs including TβMCA ( Oteng et al., 2021 ), TCA ( Azzimato et al., 2021 ) and TCDCA ( Zhang et al., 2021a ) and TωMCA ( Nie et al., 2012 ) were increased in obese mice, the phenomenon was also shown in other studies, as these BAs were considered toxic for hepatic cells owing to the increase of oxidative stress and cell apoptosis. UDCA is extensively used for the treatment of many hepatobiliary diseases such as cholestatic liver diseases and non-alcoholic steatohepatitis because of its positive effects on steatosis and inflammation ( Dong et al., 2021 ). Studies have revealed that taurine-conjugated UDCA could increase insulin sensitivity in muscle, liver, and white adipose tissue of obese humans and mice ( Schattenberg et al., 2021 ).…”

Isoliquiritin treatment of osteoporosis by promoting osteogenic differentiation and autophagy of bone marrow mesenchymal stem cells

“…In pharmacodynamic experiments, positive control drugs are used to evaluate whether the efficacy of the target drug exceeds that of clinically available drugs. Nevertheless, a positive control group is not necessary for every trial (Dong et al, 2021; Liu et al, 2022). Typically, a positive control group is used when the results of a drug trial are inconclusive.…”