Roles of hepatic stellate cells in NAFLD: From the perspective of inflammation and fibrosis

Abstract

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common diseases and severe problems worldwide because of the global increase in obesity, dyslipidemia, hypertension, and type 2 diabetes mellitus. NAFLD includes a wide spectrum of liver diseases, the histological forms of which range from non-alcoholic fatty liver (NAFL), which is generally nonprogressive, to non-alcoholic steatohepatitis (NASH), which can progress to chronic hepatitis, liver cirrhosis (LC), and sometimes hepatocellular carcinoma (HCC). Unlike NAFL, as the progressive form of NAFLD, NASH is characterized by the presence of inflammation with or without fibrosis in addition to hepatic steatosis. Although it is widely known and proved that persistent hepatic injury and chronic inflammation in the liver activate quiescent hepatic stellate cells (HSCs) and lead to hepatic fibrosis, the three-step process of “inflammation-fibrosis-carcinoma” in NAFLD has not been investigated and clarified clearly. In this process, the initiation of inflammation in the liver and the function of various liver inflammatory cells have been discussed regularly, while the activated HSCs, which constitute the principal cells responsible for fibrosis and their cross-talk with inflammation, seem not to be investigated specifically and frequently. Also, accumulated evidence suggests that HSCs can not only be activated by inflammation but also participate in the regulation of liver inflammation. Therefore, it is necessary to investigate the unique roles of HSCs in NAFLD from the perspective of inflammation and fibrosis. Here, we review the pivotal effects and mechanisms of HSCs and highlight the potential value of HSC-targeted treatment methods in NAFLD.

Promotion of liver fibrosis by Y-box binding protein 1 via the attenuation of transforming growth factor-beta 3 transcription

“…The fibrosis-initiating stimulus acts on HSCs and induces cytokine and inflammatory factor production, resulting in the primary stimulation response ( 33 , 34 ). The activated HSCs then amplify this fibrosis-initiating stimulus and further activate the surrounding cells; however, the underlying mechanism for this signaling is not well understood ( 35 ).…”

Preventive effects of caffeine on nicotine plus high-fat diet-induced hepatic steatosis and gain weight: a possible explanation for why obese smokers with high coffee consumption tend to be leaner

“…HFD-induced hepatic lipid accumulation triggers an inflammatory response, characterised by pro-inflammatory cytokine release and macrophage activation (43) . Excessive lipid decomposition generates free fatty acids, causing lipotoxicity and hepatocyte apoptosis (44) . Inflammatory cytokines like IL-1 β , IL-6, TNF- α and IL-10 contribute to hepatic steatosis and inflammation (45) .…”

Sasa veitchii extract alleviates nonalcoholic steatohepatitis in methionine–choline deficient diet‐induced mice by regulating peroxisome proliferator‐activated receptor alpha

“…Nonalcoholic steatohepatitis (NASH), a progressive form of nonalcoholic fatty liver disease (NAFLD), is an inflammatory disorder characterized by liver inflammation, excessive triglyceride (TG) levels, fibrosis, and hepatocellular injury [1]. It is the most common chronic liver disease and affects approximately 25% of the global population [2].…”