Extrahepatic Upregulation of Transforming Growth Factor Beta 2 in HCV Genotype 4-Induced Liver Fibrosis

Abstract

Elevated levels of transforming growth factor-β (TGF-β) family mediate myofibroblast generation and extracellular matrix deposition, thus making TGF-β recognized as major profibrogenic cytokines. In this article, we provide evidence that extrahepatic TGF-β2 expression at RNA and protein levels in peripheral leucocytes and serum, respectively, correlate with hepatic fibrogenesis. Current study includes a total of 110 subjects [89 naive hepatitis C virus (HCV)-infected patients (f0-f4) and 21 healthy controls]. Array profiling of 84 fibrosis-related transcripts revealed that TGF-β2 RNA was significantly upregulated compared with controls. Transcription results were confirmed by specific qRT-PCR on TGF-β2 RNA in peripheral leucocytes and TGF-β2 protein by ELISA in serum. PCR array and qRT-PCR for TGF-β2 RNA in peripheral leucocytes revealed that HCV-infected patients, regardless of the degree of fibrosis, had significantly elevated TGF-β2 RNA levels compared with controls (P = 0.018 and 0.047, respectively). This extrahepatic upregulation of TGF-β2 RNA was confirmed by elevated levels of secretory TGF-β2 protein in infected sera (P = 0.001). The Area Under the Curve of the receiver operating characteristic curve for the TGF-β2 protein between patients and controls was 0.80, a value that renders serum TGF-β2 protein a promising biomarker for liver fibrosis.