Important roles played by TGF‐β in hepatitis B infection

Abstract

Hepatitis B virus (HBV) which includes, fulminant, acute, chronic, asymptomatic, and occult HBV infection is the most prevalent virus that leads to human liver diseases. Chronic, asymptomatic, and occult infection can induce further sever diseases such as hepatocellular carcinoma (HCC) and cirrhosis of the liver. The underlying mechanisms that allow progression of the prolonged forms of the infection and subsequent HCC or cirrhosis of the liver are yet to be clarified. However, many researchers have suggested that immunological and genetic parameters may play important roles in the etiology of hepatitis B. Transforming growth factor beta (TGF-β) is an important cytokine with dual regulatory functions in the immune system and in the responses against viral infections. However, the pathways and mechanisms controlling these are not fully understood. The crucial roles of TGF-β in the development of Th17 and T regulatory lymphocytes, the main cell types involved in autoimmunity and destructive immune related diseases, have been documented and this provides insights into TGF-β function during hepatitis infection and subsequent HCC and cirrhosis of the liver. Recent findings also confirm that TGF-β directly alters hepatocyte function during hepatitis B, hence, the aim of this review is to address the current data regarding the association and status of TGF-β with hepatitis B infection and its related disorders including HCC and cirrhosis of the liver.

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

“…In human studies, serum TGF-b levels are increased in patients with HBV or hepatitis C virus (HCV), which contributes to the liver fibrosis often seen with these chronic viral infections (Alatrakchi et al 2007;Khorramdelazad et al 2012;Karimi-Googheri et al 2014). Furthermore, TGFB1 genetic polymorphisms have been associated with higher systemic TGF-b levels and worse outcome in hepatic viral infections (Dai et al 2008;Pereira et al 2008).…”

Prospective evidence of a circulating microRNA signature as a non-invasive marker of hepatocellular carcinoma in HBV patients

“…We conducted in silico analyses and found that the TGF-β signaling pathway is at the top of the list of canonical pathways regulated by the significant miRNAs identified in our study. TGF-β protein modulates a broad spectrum of cellular processes [39], has dual regulatory functions in the immune system, and is activated in response to viral infection, such as HBV [40]. Indeed, an initial step triggering HCC in HBV-infected patients is epithelial-to-mesenchymal transformation, which is modulated by TGF-β [41].…”

Molecular cloning, characterization and expression analysis of TGF-β and receptor genes in the woodchuck model

“…Furthermore, TGF-β may facilitate indirect apoptosis of hepatocytes by inducing liver fibrosis and Th17 differentiation (20). The vital role of TGF-β in balancing differentiation of pro and anti-inflammatory cells leads to conflicting results of its role on the fate of HBV infection (21). However, only limited sequences information was available for woodchuck TGF-β family.…”