Role of canonical Hedgehog signaling pathway in liver

Gao, Lili; Zhang, Zhenya; Zhang, Peng; Yu, Minghua; Yang, Tao

doi:10.7150/ijbs.28089

Cited by 58 publications

(36 citation statements)

References 107 publications

(132 reference statements)

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“…Hedgehog (Hh) is a developmental regulator discovered firstly in modulating embryonic morphogenesis [ 65 ]. Besides, Hh signaling is also involved in wound healing in adult tissues [ 66 ]. The Hh signaling is activated when Hh ligands interact with receptor Patch (Ptch) on the membrane of Hh-responsive cells.…”

Section: Autophagy and Nlrp3 Inflammasome Activate Hscs Via Hedgehmentioning

confidence: 99%

The Role of Autophagy and NLRP3 Inflammasome in Liver Fibrosis

Tao

Wang

Qiu

et al. 2020

BioMed Research International

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Liver fibrosis is an intrinsic repair process of chronic injury with excessive deposition of extracellular matrix. As an early stage of various liver diseases, liver fibrosis is a reversible pathological process. Therefore, if not being controlled in time, liver fibrosis will evolve into cirrhosis, liver failure, and liver cancer. It has been demonstrated that hepatic stellate cells (HSCs) play a crucial role in the formation of liver fibrosis. In particular, the activation of HSCs is a key step for liver fibrosis. Recent researches have suggested that autophagy and inflammasome have biological effect on HSC activation. Herein, we review current studies about the impact of autophagy and NOD-like receptors containing pyrin domain 3 (NLRP3) inflammasome on liver fibrosis and the underlying mechanisms.

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Section: Autophagy and Nlrp3 Inflammasome Activate Hscs Via Hedgehmentioning

confidence: 99%

The Role of Autophagy and NLRP3 Inflammasome in Liver Fibrosis

Tao

Wang

Qiu

et al. 2020

BioMed Research International

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“…Studies have revealed that Shh pathway activity is associated with the regulation of cholangiocyte and HSPC cell fate 12,13 . Active Shh signaling can activate genes that include targets involved in proliferation (eg, Cyclin‐D1 , MyC ) and stem cell self‐renewal (eg, Nanog , Sox9 ) 11 . Treatment of Shh ligands with EpCAM‐positive cells can promote the viability of hepatic progenitors and maintain the stemness of these progenitors in vitro 34 .…”

Section: Discussionmentioning

confidence: 99%

“…Sonic hedgehog (Shh) and Hippo‐Yes‐associated protein 1 (Yap1) activity are barely detectable in healthy livers but are markedly upregulated during injury‐induced liver regeneration 9‐11 . Furthermore, that the Shh and Yap signaling pathways are reportedly correlated with regulation of ductular reaction cell fate 12‐15 .…”

Section: Introductionmentioning

confidence: 99%

Shh‐Yap signaling controls hepatic ductular reactions in CCl₄‐induced liver injury

Jin

Huang

et al. 2020

Environmental Toxicology

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Carbon tetrachloride (CCl4) exposure can induce hepatic ductular reactions. To date, however, the related mechanism remains largely unknown. Sonic hedgehog (Shh) and Yes‐associated protein (Yap) signaling are correlated with liver injury and regeneration. Herein, we investigated the role of Shh and Yap signaling in the fate of ductular reaction cells in CCl4‐treated livers and the possible mechanisms. Wild‐type and Shh‐EGFP‐Cre male mice were exposed to CCl4 (2 mL/kg), and then treated with or without the Shh signaling inhibitor Gant61. The level of liver injury, proliferation of ductular reaction cells, and expression levels of mRNA and protein related to the Shh and Yap signaling components were assessed. Results showed that CCl4 treatment induced liver injury and promoted activation and proliferation of ductular reaction cells. In addition, CCl4 induced the expression of Shh ligands in hepatocytes, accompanied by activation of Shh and Yap1 signaling in the liver. Furthermore, administration of Gant61 ameliorated liver regeneration, inhibited hepatic ductular reactions, and decreased Shh and Yap1 signaling activity. Thus, Shh‐Yap1 signaling appears to play an integral role in the proliferation of ductular reaction cells in CCl4‐induced liver injury. This study should improve our understanding of the mechanism of CCl4‐induced liver injury and ductular reactions and provide support for future investigations on liver disease therapy.

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“…In turn, HH signaling, a recently reported inhibitory target of GPR39 [42], was indicated to suppress HBV replication. HH signaling has been demonstrated to play a substantial role in hepatocarcinogenesis and HCC progression [79][80][81][82]. On the other hand, AKT, an oncogenic kinase for hepatocyte survival, was activated by HBx and inhibited HBV replication, indicative of viral tactics for immune evasion and persistent production of progeny at the cost of high viral replication [83].…”

Section: Discussionmentioning

confidence: 99%

Orchestration of Intracellular Circuits by G Protein-Coupled Receptor 39 for Hepatitis B Virus Proliferation

Goto¹,

Nishitsuji²,

Sugiyama³

et al. 2020

IJMS

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Hepatitis B virus (HBV), a highly persistent pathogen causing hepatocellular carcinoma (HCC), takes full advantage of host machinery, presenting therapeutic targets. Here we aimed to identify novel druggable host cellular factors using the reporter HBV we have recently generated. In an RNAi screen of G protein-coupled receptors (GPCRs), GPCR39 (GPR39) appeared as the top hit to facilitate HBV proliferation. Lentiviral overexpression of active GPR39 proteins and an agonist enhanced HBV replication and transcriptional activities of viral promoters, inducing the expression of CCAAT/enhancer binding protein (CEBP)-β (CEBPB). Meanwhile, GPR39 was uncovered to activate the heat shock response, upregulating the expression of proviral heat shock proteins (HSPs). In addition, glioma-associated oncogene homologue signaling, a recently reported target of GPR39, was suggested to inhibit HBV replication and eventually suppress expression of CEBPB and HSPs. Thus, GPR39 provirally governed intracellular circuits simultaneously affecting the carcinopathogenetic gene functions. GPR39 and the regulated signaling networks would serve as antiviral targets, and strategies with selective inhibitors of GPR39 functions can develop host-targeted antiviral therapies preventing HCC.

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Role of canonical Hedgehog signaling pathway in liver

Cited by 58 publications

References 107 publications

The Role of Autophagy and NLRP3 Inflammasome in Liver Fibrosis

The Role of Autophagy and NLRP3 Inflammasome in Liver Fibrosis

Shh‐Yap signaling controls hepatic ductular reactions in CCl₄‐induced liver injury

Orchestration of Intracellular Circuits by G Protein-Coupled Receptor 39 for Hepatitis B Virus Proliferation

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Role of canonical Hedgehog signaling pathway in liver

Cited by 58 publications

References 107 publications

The Role of Autophagy and NLRP3 Inflammasome in Liver Fibrosis

The Role of Autophagy and NLRP3 Inflammasome in Liver Fibrosis

Shh‐Yap signaling controls hepatic ductular reactions in CCl4‐induced liver injury

Orchestration of Intracellular Circuits by G Protein-Coupled Receptor 39 for Hepatitis B Virus Proliferation

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Shh‐Yap signaling controls hepatic ductular reactions in CCl₄‐induced liver injury