Neurotrophic factors stimulate the activation of hepatic stellate cells in liver fibrosis.

BACKGROUND AND AIMS: Patients with liver fibrosis who have pain in the liver region may have changed nerve factors. The expression of neurokines and hepatic nerves in liver fibrosis, however, was little understood. In order to better understand how liver fibrosis develops, we plan to look into the hepatic nerve and neurokine changes and how they relate to hepatic stellate cells (HSCs). METHODS: The expression of neurokines in liver samples from 55 chronic hepatitis B patients and the carbon tetrachloride (CCl4) animal model were studied. The co-staining of Nissl and α-SMA allowed us to investigate the neurons and their interaction with α-SMA in fibrotic livers, as well as the expression of the glial cell marker glial fibrillary acidic protein (GFAP) and its relationship with α-SMA, a marker of HSCs. SH-SY5Y cells were treated with a fibrotic serum to imitate the hepatic microenvironment on neuronal cells. We also used brain-derived neurotrophic factor (BDNF) to stimulate mouse primary HSCs and LX2. RESULTS: The levels of mRNA for neurokines such as BDNF, GFAP, and growth-associated protein (GAP43) are significantly increased in both human and animal liver fibrosis. As liver fibrosis advances, we found that Nissl bodies and α-SMA may co-localize, suggesting a connection between hepatic nerves and HSCs. Human fibrotic serum may increase neurkines, notably BDNF, in SH-SY5Y cells. We also found that BDNF increased pro-inflammatory cytokines and fibrogenic markers in hHSCs. CONCLUSIONS: Patients with hepatic fibrosis had significantly higher levels of BDNF, GFAP, GAP43, and nerve fibers. HSC and nerve fibers interact, and nerves also create neurogenic substances that promote liver fibrosis and HSC activation.

Peroxisome proliferator-activated receptor γ inhibits hepatic stellate cell activation regulated by miR-942 in chronic hepatitis B liver fibrosis.

AIMS: Liver fibrosis is a chronic liver disease characterized by hepatic stellate cell (HSC) activation. Peroxisome proliferator-activated receptor gamma (PPARγ) play an important role in HSC activation. This study aimed to investigate the role of PPARγ in the progression of human hepatic fibrosis and the mechanism by which microRNA-942 regulates HSC activation. METHODS: 70 chronic hepatitis B (CHB) patients liver tissues were used to assess PPARγ, α-SMA and miR-942 levels by immunoblot and real-time PCR. Human primary HSCs or LX2 cells were used to perform multiple molecular experiments based on the transfection of small interfering RNA (siRNA) or co-transfection of microRNA inhibitor. Site-directed mutagenesis and luciferase reporter assays were used to identify miR-942 targets. miR-942 expression and localization in hepatic fibrosis and co-localization between α-SMA were determined by fluorescence in situ hybridization (FISH). KEY FINDINGS: The mRNA expression of PPARγ was decreased in activated HSCs and CHB patients with liver fibrosis, which was negatively correlated with F stage and α-SMA. miR-942 negatively regulates PPARγ expression via targeting the PPARγ 3'UTR. Inhibiting PPARγ promoted TGFß1 induced HSC activation, and this effect was blocked after inhibiting the miR-942. Moreover, miR-942 was mainly expressed in fibrous septa and negatively correlated with PPARγ in liver fibrosis. SIGNIFICANCE: PPARγ targeting by miR-942 and decreasing HSC activation in human hepatic fibrosis. Hence, regulating PPARγ may be a promising therapeutic strategy for hepatic fibrosis.

[Progress on magnetic resonance imaging for evaluating the articular cartilage of the knee joint].

The reasonable selection of magnetic resonance imaging(MRI) scan sequence and parameters is very important for the objective evaluation of the results of clinical study and high quality imaging. The semi quantitative scoring system of total knee joint including Whole Organ Magnetic Resonance Imaging Score, Boston Leeds Osteoarthritis Knee Score, MRI Osteoarthritis Knee Score, Cartilage Repair Osteoarthritis Knee Score and so on. They can fully evaluate the imaging changes of various organs during the development of knee osteoarthritis. With the continuous development of MRI technology, the morphological and physiological changes of articular cartilage can be quantitatively assessed. T2 mapping, Diffusion Weighted Imaging, and delayed Gadolinium-Enhanced MRI of Cartilage can be quantitatively monitoring changes in cartilage matrix components. These quantitative and semi quantitative evaluation techniques are helpful to detect OA in its early stage, guide clinical early intervention, and also provide the possibility for the accurate evaluation of the therapeutic effect.