Role of Hedgehog Signaling Pathway in NASH.
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.
Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. mverdelhomachado@gmail.com.|Gastroenterology Department, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte (CHLN), Lisboa 1649-035, Portugal. mverdelhomachado@gmail.com.
Mariana
M
Verdelho Machado
Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. diehl004@mc.duke.edu.
Anna Mae
AM
Diehl
D000818:Animals; D004195:Disease Models, Animal; D053823:Hedgehog Proteins; D006801:Humans; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D015398:Signal Transduction; D014945:Wound Healing
D053823:Hedgehog Proteins
hedgehog pathway; nonalcoholic fatty liver disease; wound-healing response