RESUMO
Liver fibrosis has the potential to progress into liver cirrhosis, liver failure, and even death. Hepatic stellate cells (HSCs) activation play a central role in liver fibrosis, and persistently damaged hepatocytes secrete soluble factors that activate transdifferentiation of HSCs into myofibroblasts. Our previous studies indicated that fine particulate matter (PM2.5) can activate HSCs by stimulating hepatocytes to secrete TGF-ß1. However, whether PM2.5 activates HSCs by regulating oxidative stress in hepatocytes remains uncertain. Oleanolic acid (OA) has been widely used in the clinic for hepatoprotection in Chinese medicine. In the present study, OA-loaded nanoparticles (OA-NP) with high solubility were used to attenuate the activation of HSCs induced by PM2.5-treated hepatocytes, and further studies were performed to explore the mechanism in which OA-NP plays a vital part. Our results showed that consistently PM2.5 treatment induced oxidative stress in hepatocytes. Moreover, the activation of HSCs induced by PM2.5-treated hepatocytes was reversed by antioxidant N-acetylcysteine treatment. Hence, PM2.5 may participate in the activation of HSCs by regulating oxidative stress in hepatocytes. Using a co-cultivation system, our results proved pretreatment with OA-NP significantly attenuates the activation of HSCs induced by PM2.5-exposed hepatocytes. In addition, the TGF-ß1 expression and oxidative stress in hepatocytes with PM2.5 treated were reduced by the incubation with OA-NP. These observations demonstrated that OA-NP protects against the activation of HSCs by decreasing the TGF-ß1 level and oxidative stress in PM2.5-exposed hepatocytes.
Assuntos
Células Estreladas do Fígado/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Nanopartículas/química , Ácido Oleanólico/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/toxicidade , Fator de Crescimento Transformador beta1/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatócitos/metabolismo , Ácido Oleanólico/química , Tamanho da Partícula , Fator de Crescimento Transformador beta1/genéticaRESUMO
The interaction between various types of hepatic cells is related to liver fibrosis. Recent studies demonstrated that fine particulate matter (PM2.5) exposure is an important risk factor for the occurrence of liver fibrosis, but its molecular mechanism is still obscure. In this study, we aimed to investigate whether transforming growth factor- ß1 (TGF- ß1) secreted from PM2.5-treated hepatocytes (L-O2) are shuttled to hepatic stellate cells (HSCs) and to establish their effects on HSCs. We have observed that the conditioned medium from L-O2 cells stimulated with PM2.5 induced the activation of LX-2 cells, and at the same time, the same results were obtained when we co-cultured LX-2 in PM2.5-exposed L-O2 cells. In addition, analysis of L-O2 cells stimulated with PM2.5 revealed significant increases in TGF-ß1 expression. Moreover, we found that the TGF-ß1 receptor inhibitor, SB-525334, decreases the proliferation and migration of LX-2 cells in the co-culture system. In addition, the expression of α-smooth muscle actin and type I collagen in LX-2 cells induced by PM2.5-treated L-O2 cells were also blocked by pretreated with SB-525334. These observations imply that PM2.5 induces TGF- ß1expression in hepatocytes, which leads to HSCs activation.