Abstract
BackgroundPRC1 (Protein regulator of cytokinesis 1) regulates microtubules organization and functions as a novel regulator in Wnt/β-catenin signaling pathway. Wnt/β-catenin is involved in development of liver fibrosis (LF). We aim to investigate effect and mechanism of PRC1 on liver fibrosis.MethodsCarbon tetrachloride (CCl4)-induced mice LF model was established and in vitro cell model for LF was induced by mice primary hepatic stellate cell (HSC) under glucose treatment. The expression of PRC1 in mice and cell LF models was examined by qRT-PCR (quantitative real-time polymerase chain reaction), western blot and immunohistochemistry. MTT assay was used to detect cell viability, and western blot to determine the underlying mechanism. The effect of PRC1 on liver pathology was examined via measurement of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and hydroxyproline, as well as histopathological analysis.ResultsPRC1 was up-regulated in CCl4-induced mice LF model and activated HSC. Knockdown of PRC1 inhibited cell viability and promoted cell apoptosis of activated HSC. PRC1 expression was regulated by Wnt3a signaling, and PRC1 could regulate downstream β-catenin activation. Moreover, PRC1 could activate glioma-associated oncogene homolog 1 (GLI1)-dependent osteopontin expression to participate in LF. Adenovirus-mediated knockdown of PRC1 in liver attenuated LF and reduced collagen deposition.ConclusionsPRC1 aggravated LF through regulating Wnt/β-catenin mediated GLI1-dependent osteopontin expression, providing a new potential therapeutic target for LF treatment.
Highlights
Liver fibrosis (LF) is a common pathological process of many chronic liver diseases developing to cirrhosis and liver cancer with high morbidity and mortality rate [1]
Over-expression of Protein regulator of cytokinesis 1 (PRC1) demonstrated the reversed effects on protein expression (Fig. 3c). These results revealed that knockdown of PRC1 suppressed cell proliferation and promoted cell apoptosis of activated hepatic stellate cell (HSC), might attenuate liver fibrosis (LF)
PRC1 was up‐regulated in carbon tetrachloride (CCl4)‐induced mice LF To determine regulation ability of PRC1 in LF, mice model via CCl4 treatment was established
Summary
Liver fibrosis (LF) is a common pathological process of many chronic liver diseases developing to cirrhosis and liver cancer with high morbidity and mortality rate [1]. Microtubule (MT) is crucial for cell growth, cell cycle and migration [9]. PRC1 is widely known as prognostic biomarker in lung squamous cell carcinoma [16], bladder cancer [14] and breast cancer [17], which could promote tumor cell proliferation and migration. Knockdown of PRC1 was shown to inhibit cell proliferation of hepatocellular carcinoma [18]. PRC1 (Protein regulator of cytokinesis 1) regulates microtubules organization and functions as a novel regulator in Wnt/β-catenin signaling pathway. Wnt/β-catenin is involved in development of liver fibrosis (LF). We aim to investigate effect and mechanism of PRC1 on liver fibrosis
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