An Overview of Hedgehog Signaling in Fibrosis

Hu, Liping; Lin, Xiangyang; Lu, Hong; Chen, Bicheng; Bai, Yongheng

doi:10.1124/mol.114.095141

Cited by 74 publications

(66 citation statements)

References 139 publications

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“…For example, Jung et al (2015) reported that SHH pathway activation was observed, especially in the cholangiocytes of the peribiliary glands, in human patients with biliary atresia. In pathological studies, some have reported that Hh expression is considerably increased in fibrotic damaged biliary diseases in response to injury (Omenetti et al, 2008;Omenetti and Diehl, 2011;Cui et al, 2013;Hu et al, 2015). It has also been speculated that the SHH signaling pathway regulates the epithelial-mesenchymal transition of cholangiocytes (Omenetti et al, 2008;Jung et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Embryonic cholecystitis and defective gallbladder contraction in the Sox17-haploinsufficient mouse model of biliary atresia

et al. 2017

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The gallbladder excretes cytotoxic bile acids into the duodenum through the cystic duct and common bile duct system. Sox17 haploinsufficiency causes biliary atresia-like phenotypes and hepatitis in late organogenesis mouse embryos, but the molecular and cellular mechanisms underlying this remain unclear. In this study, transcriptomic analyses revealed the early onset of cholecystitis in Sox17 +/− embryos, together with the appearance of ectopic cystic duct-like epithelia in their gallbladders. The embryonic hepatitis showed positive correlations with the severity of cholecystitis in individual Sox17+/− embryos. Embryonic hepatitis could be induced by conditional deletion of Sox17 in the primordial gallbladder epithelia but not in fetal liver hepatoblasts. The Sox17 +/− gallbladder also showed a drastic reduction in sonic hedgehog expression, leading to aberrant smooth muscle formation and defective contraction of the fetal gallbladder. The defective gallbladder contraction positively correlated with the severity of embryonic hepatitis in Sox17 +/− embryos, suggesting a potential contribution of embryonic cholecystitis and fetal gallbladder contraction in the early pathogenesis of congenital biliary atresia.

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Section: Discussionmentioning

confidence: 99%

Embryonic cholecystitis and defective gallbladder contraction in the Sox17-haploinsufficient mouse model of biliary atresia

et al. 2017

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“…Gli proteins are transcription factors that belong to the Kruppel-like family and contain a zinc-finger DNA-binding domain (Hu et al, 2015). Mammals have 3 Gli proteins: Gli-1, Gli-2 and Gli-3.…”

Section: The Hedgehog Signaling Pathwaymentioning

confidence: 99%

The hedgehog pathway in nonalcoholic fatty liver disease

Machado

Diehl

2018

Critical Reviews in Biochemistry and Molecular Biology

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Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of obesity-associated liver diseases and it has become the major cause of cirrhosis in the Western world. The high prevalence of NAFLD-associated advanced liver disease reflects both the high prevalence of obesity-related fatty liver (hepatic steatosis) and the lack of specific treatments to prevent hepatic steatosis from progressing to more serious forms of liver damage, including nonalcoholic steatohepatitis (NASH), cirrhosis, and primary liver cancer. The pathogenesis of NAFLD is complex, and not fully understood. However, compelling evidence demonstrates that dysregulation of the hedgehog (Hh) pathway is involved in both the pathogenesis of hepatic steatosis and the progression from hepatic steatosis to more serious forms of liver damage. Inhibiting Hedgehog signaling enhances hepatic steatosis, a condition which seldom results in liver-related morbidity or mortality. In contrast, excessive Hedgehog pathway activation promotes development of NASH, cirrhosis, and primary liver cancer, the major causes of liver-related deaths. Thus, suppressing excessive Hh pathway activity is a potential approach to prevent progressive liver damage in NAFLD. Various pharmacologic agents that inhibit Hh signaling are available and approved for cancer therapeutics; more are being developed to optimize the benefits and minimize the risks of inhibiting this pathway. In this review we will describe the Hh pathway, summarize the evidence for its role in NAFLD evolution, and discuss the potential role for Hh pathway inhibitors as therapies to prevent NASH, cirrhosis and liver cancer.

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“…88,89 They will proliferate, migrate, and secrete ECM proteins, thus leading to pancreatic fibrosis. 90,91 Fibrogenesis will appear approximately during the onset of a lesion. Hedgehog signaling induces progressive pancreatic fibrosis intermingled with proliferating ductal structures that are accompanied by the destruction of acinar structures.…”

Section: Introductionmentioning

confidence: 99%

Hedgehog Signaling in Pancreatic Fibrosis and Cancer

Bai

Dong

et al. 2016

Medicine

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The hedgehog signaling pathway was first discovered in the 1980s. It is a stem cell-related pathway that plays a crucial role in embryonic development, tissue regeneration, and organogenesis. Aberrant activation of hedgehog signaling leads to pathological consequences, including a variety of human tumors such as pancreatic cancer. Multiple lines of evidence indicate that blockade of this pathway with several small-molecule inhibitors can inhibit the development of pancreatic neoplasm. In addition, activated hedgehog signaling has been reported to be involved in fibrogenesis in many tissues, including the pancreas. Therefore, new therapeutic targets based on hedgehog signaling have attracted a great deal of attention to alleviate pancreatic diseases. In this review, we briefly discuss the recent advances in hedgehog signaling in pancreatic fibrogenesis and carcinogenesis and highlight new insights on their potential relationship with respect to the development of novel targeted therapies.

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An Overview of Hedgehog Signaling in Fibrosis

Cited by 74 publications

References 139 publications

Embryonic cholecystitis and defective gallbladder contraction in the Sox17-haploinsufficient mouse model of biliary atresia

Embryonic cholecystitis and defective gallbladder contraction in the Sox17-haploinsufficient mouse model of biliary atresia

The hedgehog pathway in nonalcoholic fatty liver disease

Hedgehog Signaling in Pancreatic Fibrosis and Cancer

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