Paeoniflorin alleviates liver fibrosis by inhibiting HIF-1α through mTOR-dependent pathway

α5-nAChR modulates nicotine-induced cell migration and invasion in A549 lung cancer cells

“…Recently, genome wide association studies have indicated that a5-nAChR is highly associated with lung cancer risk and nicotine dependence (Boezen 2009;Macqueen et al, 2014;Zhao et al, 2014). In our previous study, the results suggest that a5-nAChR expression was correlated with the clinical TMN stage of lung cancer.…”

Suppression of Thioacetamide-Induced Hepatic Injury in Rats treatment with Resveratrol: Role of mammalian Target of Rapamycin (mTOR) Cell Signaling

“…The quiescent, nonproliferative hepatic stellate cells (HSCs) become highly proliferative upon exposing to insults causing these cells producing most of the extracellular matrix (ECM) in the fibrotic liver via the upregulation of mTOR (Neef et al, 2006;Shan et al, 2016). Activated mTOR leads to many downstream cell signalling pathways including the activation of hypoxic transcription factor, HIF-1α, which participates in promoting liver fibrosis (Zhao et al, 2014) and cancer (Masoud & Li, 2015). The hepatotoxic agents, TAA and CCl4 are reported to activate the mTOR-HIF-1α axis in many animal models of liver diseases and HSCs cell lines (Zhao et al;Wu et al, 2016).…”

“…Activated mTOR leads to many downstream cell signalling pathways including the activation of hypoxic transcription factor, HIF-1α, which participates in promoting liver fibrosis (Zhao et al, 2014) and cancer (Masoud & Li, 2015). The hepatotoxic agents, TAA and CCl4 are reported to activate the mTOR-HIF-1α axis in many animal models of liver diseases and HSCs cell lines (Zhao et al;Wu et al, 2016). Furthermore, these agents are also known to augment profibrogenic and inflammatory biomarkers such as α-SMA that upregulates fibroblast activity leading to the production of collagen and other fibers (Nouchi et al, 1991;Zhao et al;Wu et al), and TNF-α (Morio et al, 2001).…”

Metformin inhibits mTOR–HIF‐1α axis and profibrogenic and inflammatory biomarkers in thioacetamide‐induced hepatic tissue alterations

“…Activated mTOR leads to many downstream cell signaling pathways including the activation of hypoxic transcription factor, HIF‐1α, which participates in promoting liver fibrosis (Zhao et al, ) and cancer (Masoud & Li, ). The hepatotoxic agents, TAA, and carbon tetrachloride (CCl 4 ) are reported to activate the mTOR–HIF‐1α axis in many animal models of liver diseases and HSCs cell lines (Wu et al, ; Zhao et al, ). Furthermore, these agents are also known to augment profibrogenic and inflammatory biomarkers such as (a) α‐SMA that upregulates fibroblast activity leading to the production of collagen and other fibers (Nouchi, Tanaka, Tsukada, Sato, & Marumo, ; Wu et al, ; Zhao et al, ); (b) tissue inhibitor of metalloproteinases‐1 (TIMP‐1), a natural inhibitor of matrix metalloproteinases (MMPs) that prevents the degradation of ECM (Huang et al, ; Park, Shin, Lee, Lee, & Jang, ; Roderfeld et al, ) and hence promotes fibrosis to occur; and (c) tumor necrosis factor‐α (TNF‐α; Morio et al, ; Roderfeld et al, ).…”