BMC Molecular and Cell Biology最新文献

Background: Clinical and preclinical evidence suggests that inflammation is closely associated with various arterial diseases. Multiple studies have reported the effects of statins on different cell types, yet the effects of atorvastatin (ATV) and its mechanisms on inflamed HUVECs' cellular responses are still under investigation. This study investigates how different doses of ATV affect inflammatory responses, extracellular matrix (ECM) regulators, and cell migration capacity assessed by an in vitro scratch wound closure assay in lipopolysaccharide (LPS) stimulated endothelial cells.

Methods: ATV was applied to cells at different doses (5-10-50 µM) with or without LPS (20 ng/mL). Cell proliferation and toxicity were investigated in the indicated groups. Then, the possible effects of ATV on MMP-2, MMP-9, TIMP-1,TIMP-2 expression levels, scratch-closure (cell migration) time were examined. Gene expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 was quantified by qPCR, while protein levels were determined by Western blotting. Cell migration was evaluated using a scratch assay and real-time imaging system.

Results: High-dose ATV was more cytotoxic, while wound closure times showed a numerical increase that did not reach statistical significance under LPS stimulation. While low-dose ATV increased MMP and TIMP expressions, high-dose treatment reduced TIMP-1 and disturbed the MMP/TIMP balance. This imbalance was accompanied by reduced cellular recovery capacity under inflammatory stress.

Conclusions: This study highlights the complex cellular effects of ATV under inflammatory conditions, supporting its context- and dose-dependent role in endothelial cell behavior and matrix regulation. These findings highlight the importance of dosage optimization in therapeutic contexts targeting vascular inflammation and provide novel insight into how statin dosing influences endothelial recovery mechanisms, beyond cholesterol regulation.

Background: Huntingtin (HTT) is an important gene for cellular processes such as autophagy, and its loss leads to neurodegenerative disease phenotypes. In Dictyostelium discoideum, HTT-null (htt-) cells exhibit impaired basal autophagy and fail to develop in the presence of ammonium chloride.

Results: Here we conducted a mutagenesis screen on htt- cells to identify potential genetic suppressors of the htt- phenotype. A mutant strain was isolated that counteracts many of the hallmark defects engendered with htt loss. This mutant, htt-;supX, rescues the growth, cargo degradation defects, developmental timing, and autophagic flux of htt- cells under ammonium chloride stress, representing a partial rescue of the htt- phenotype. Whole-genome sequencing revealed four mutations in the mutant strain affecting genes involved in vesicle trafficking, signal transduction, metal ion regulation, and fatty acid elongation. Transcriptome sequencing further identified 208 differentially expressed genes in the mutant strain, including genes whose expression was returned to wild-type levels, suggesting a potential mechanism by which htt-;supX mediates phenotypic recovery. Among these, five genes have known autophagy-related functions and may be implicated in pathways such as Rab GTPase regulation and SNARE-mediated vesicle fusion.

Conclusions: Our study highlights the ability of second-site mutations to restore autophagic function in the absence of HTT and identifies candidate genes and pathways for further investigation into Huntington's Disease models and autophagy modulation.