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.
Dnase2<sup>-/-</sup> Ifnar<sup>-/-</sup> mice were shown to recapitulate many features of the DNase II-deficient patients including cytopenia, extramedullary hematopoiesis and liver fibrosis.
In this study, complimentary in vivo and in vitro approaches were used: (1) CCl<sub>4</sub> -induced LF model in wild type (WT), Fgf15<sup>-/-</sup> , and Fgf15 transgenic (TG) mice with BA levels modulated by feeding cholestyramine- or cholic acid-containing diets; (2) analysis of primary HSCs isolated from WT and Fgf15<sup>-/-</sup> mice; and (3) treatment of a human HSC line, LX-2, with FXR activators and/or recombinant FGF19 protein.
In patients with nonalcoholic steatohepatitis (NASH), PNPLA3 GG compared to CC was associated with higher AST levels [38.4±25.3 versus 36.7±40.1IU/L, p=0.0395)] and with the presence of liver fibrosis (≥F2 fibrosis, p=0.0272).
In vivo, we found that IL-10 gene by hydrodynamics-based transfection attenuated CCL<sub>4</sub>-induced liver fibrosis associated with senescence of activated HSCs in rats.
LDH was significantly associated with advanced liver fibrosis (FIB-4 aOR = 22.22 [1.22-403.72]) only among HIV/HCV+ participants with an LDH of 100-600 kg.
Liver fibrosis was assessed using the fibrosis-4 index (FIB-4) [age (years)× aspartate aminotransferase level (IU/L)/platelet count (10<sup>9</sup>/L)/√alanine aminotransferase (IU/L)].
The results showed that ASC transplantation alleviated liver fibrosis effectively as evidenced by reduced collagen accumulation, decreased fatty degeneration, increased hepatocyte regeneration, decreased inflammation and significantly enhanced liver function; moreover, ASCs decreased the expression of pro-fibrogenic factors including TGF-β and α-SMA.
The results showed that ASC transplantation alleviated liver fibrosis effectively as evidenced by reduced collagen accumulation, decreased fatty degeneration, increased hepatocyte regeneration, decreased inflammation and significantly enhanced liver function; moreover, ASCs decreased the expression of pro-fibrogenic factors including TGF-β and α-SMA.