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Table 1 Hypoxia-mediated HSCs activation is involved in the regulation of liver fibrosis by multiple mechanisms

From: The roles and mechanisms of hypoxia in liver fibrosis

Objects Treatments Targets Mechanisms of action in HSCs Refs
Primary HSC Cultured in 1% oxygen and 5% CO2 balanced with N2 Ca2+ Trigger Ca2+–AMPK–mTOR and PKCh activation, which leads to enhanced HSC autophagy [12]
HSC-T6 Paeoniflorin RTKs HSCs inactivation through mTOR/HIF-1α signaling pathway [9]
Cultured in 1% oxygen HIF-1α Hif-1α and MAPK co-regulate activation of HSC [10]
Rosiglitazone PPARγ sGC/cGMP/PKG and PI3K/AKT signals act on PPARγ synergistically to attenuate hypoxia-induced HSC activation [16]
LX-2 Stimulated by CoCl2 TRPC6 1. Elevation of intracellular calcium which is coupled with the activation of the calcineurin-NFAT pathway which activates the synthesis of ECM
2. Activating SMAD2/3 dependent TGF-β signaling in facilitating upregulated expression of αSMA and collagen
[11]
Cultured in 0.3% O2 and 5%CO2, at 37 °C HIF-1α A positive feedback loop between HIF-1α and GAPDH, which promoting HSCs apoptosis under hypoxic conditions [20]
Treated with EVs from hepatocytes which were treated with fatty acids and CoCl2 EVs crosstalk EVs from fat-laden hepatocytes undergoing chemical hypoxia evoke pro-fibrotic responses in LX-2 cells [17]
Stimulated by CoCl2 HIF-1α Exosomes derived by HSCs was regulated by Hif-1. Exosomes containing glycolysis related proteins were involved in the activation and metabolic switch of HSCs and other liver nonparenchymal cells [18]