Given the role of GLIS3 in transcriptional activation and repression during embryogenesis, in humans, GLIS3 mutations present with multisystem involvement that also includes renal cystic dysplasia, progressive liver fibrosis and osteopenia.
Mutations in human GLIS3 have been implicated in a syndrome characterized by neonatal diabetes and congenital hypothyroidism (NDH) and in some patients accompanied by polycystic kidney disease, glaucoma, and liver fibrosis.
Lower albumin was also associated with increased levels of several inflammatory biomarkers, markers of liver fibrosis, albuminuria, and greater arterial stiffness, diastolic dysfunction and pulmonary hypertension.
In conclusion, these findings indicated that Nano NiO induced hepatic fibrosis via TGF-β1-mediated Smad pathway activation, EMT occurrence, and ECM deposition.
Mechanistically, we demonstrated that high level of MFN2 inhibited TGF-β1/Smad signaling pathway, triggered downregulation of type I, type III, and type IV collagen, and antagonized the formation of factors associated with liver fibrosis.
The aim of this project was to develop a suitable rodent cell culture model for the investigation of key events involved in the development of liver fibrosis, specifically the responses to pathophysiological stimuli such as TGF-β1 and LPS-triggered inflammation.
Additionally, MSCs were stimulated in vitro with LF-associated factors, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and transforming growth factor-β1 (TGF-β1), to mimic the LF microenvironment.
As liver fibrosis is the consequence of hepatic stellate cell (HSC) activation, the questions were addressed whether alterations induced by high glucose concentration are directly related to TGFB1 effect, or other mechanisms are activated.
Autophagy is a self-degrading process.Previously, we showed that insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) is a novel transforming growth factor β1 (TGFβ1)-interacting factor in liver fibrosis; the role of TGFβ1-mediated autophagy in hepatic stellate cells (HSCs) activation has been investigated.
However, TIM-4 interference in the KCs inhibited Akt1-mediated ROS production, resulting in the suppression of PINK1, Parkin and LC3-II/I activation and the reduction of TGF-β1 secretion during liver fibrosis.
However, whether serum glycosylation isomer of M2BP (M2BPGi) was associated with the regression of liver fibrosis in patients with chronic hepatitis B (CHB) during IFN-α add-on therapy is still unknown.
To avoid the impact of schistosomicidal activity of PZQ against liver fibrosis induced by S. japonicum infection, we established a mouse model of carbon tetrachloride (CCl<sub>4</sub> )-induced liver fibrosis for in vivo studies and used TGF-β1-stimulated human hepatic stellate cell line (LX-2) in addition to other fibroblast-like cell line (MES13) and fibroblast cell line (NIH3T3) in vitro.
Collectively, our results reveal that SEPT6 regulates various biological behaviors in HSCs through TGF-β1/Smad, mitogen-activated protein kinases and phosphatidylinositol-3-kinase/protein kinase B signaling pathways, thus promoting liver fibrosis.
These findings suggested that AKF-PD attenuated the progression of hepatic fibrosis by suppressing HSCs activation via the TGF-β1/Smad and MAPK signaling pathways, and therefore that AKF-PD may be suitable for use as a novel therapeutic agent against liver fibrosis.
The degree of liver fibrosis was suppressed by treatment with VA-coupled liposomal ROCK inhibitor, and the expression of α-SMA and TGF-β1 in liver tissues was also significantly suppressed.
The importance of both NRF2 and p62-dependent autophagy in SPD-mediated liver protection was confirmed using a carbon tetrachloride-induced liver fibrosis model in wild-type, Nrf2<sup>-/-</sup> , p62<sup>-/-</sup> and Nrf2<sup>-/-</sup> ;p62<sup>-/-</sup> mice, as the protective effect of SPD was significantly reduced in NRF2 or p62 single knockout mice, and completely abolished in the double knockout mice.