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Role of Hedgehog Signaling Pathway in NASH

Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
Gastroenterology Department, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte (CHLN), Lisboa 1649-035, Portugal
Authors to whom correspondence should be addressed.
Academic Editors: Amedeo Lonardo and Giovanni Targher
Int. J. Mol. Sci. 2016, 17(6), 857;
Received: 22 March 2016 / Revised: 18 May 2016 / Accepted: 26 May 2016 / Published: 1 June 2016
(This article belongs to the Special Issue Non-Alcoholic Fatty Liver Disease Research 2016)
PDF [993 KB, uploaded 1 June 2016]


Non-alcoholic fatty liver disease (NAFLD) is the number one cause of chronic liver disease in the Western world. Although only a minority of patients will ultimately develop end-stage liver disease, it is not yet possible to efficiently predict who will progress and, most importantly, effective treatments are still unavailable. Better understanding of the pathophysiology of this disease is necessary to improve the clinical management of NAFLD patients. Epidemiological data indicate that NAFLD prognosis is determined by an individual’s response to lipotoxic injury, rather than either the severity of exposure to lipotoxins, or the intensity of liver injury. The liver responds to injury with a synchronized wound-healing response. When this response is abnormal, it leads to pathological scarring, resulting in progressive fibrosis and cirrhosis, rather than repair. The hedgehog pathway is a crucial player in the wound-healing response. In this review, we summarize the pre-clinical and clinical evidence, which demonstrate the role of hedgehog pathway dysregulation in NAFLD pathogenesis, and the preliminary data that place the hedgehog pathway as a potential target for the treatment of this disease. View Full-Text
Keywords: nonalcoholic fatty liver disease; hedgehog pathway; wound-healing response nonalcoholic fatty liver disease; hedgehog pathway; wound-healing response

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Verdelho Machado, M.; Diehl, A.M. Role of Hedgehog Signaling Pathway in NASH. Int. J. Mol. Sci. 2016, 17, 857.

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