Defective cholesterol biosynthesis in eye lens cells is often associated with cataracts; however, how genes involved in cholesterol biosynthesis are regulated in lens cells remains unclear. Here, we show that Quaking (Qki) is required for the transcriptional activation of genes involved in cholesterol biosynthesis in the eye lens. At the transcriptome level, lens-specific Qki-deficient mice present downregulation of genes associated with the cholesterol biosynthesis pathway, resulting in a significant reduction of total cholesterol level in the eye lens. Mice with Qki depletion in lens epithelium display progressive accumulation of protein aggregates, eventually leading to cataracts. Notably, these defects are attenuated by topical sterol administration. Mechanistically, we demonstrate that Qki enhances cholesterol biosynthesis by recruiting Srebp2 and Pol II in the promoter regions of cholesterol biosynthesis genes. Supporting its function as a transcription co-activator, we show that Qki directly interacts with single-stranded DNA. In conclusion, we propose that Qki-Srebp2-mediated cholesterol biosynthesis is essential for maintaining the cholesterol level that protects lens from cataract development.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139980PMC
http://dx.doi.org/10.1038/s41467-021-22782-0DOI Listing

Publication Analysis

Top Keywords

cholesterol biosynthesis
32
eye lens
16
cholesterol
10
biosynthesis
8
biosynthesis eye
8
lens cells
8
genes involved
8
involved cholesterol
8
cholesterol level
8
lens
7

Similar Publications

An experiment was conducted to assess the effects of the BCAA and their interactions on performance, carcass composition, lipid metabolism, liver health, and intestinal morphometry in broiler chickens. Male chickens ( = 1080) were randomly assigned into floor pens in a 3 × 3 factorial design with 3 dietary ratios of SID Leu:Lys (110, 150, and 190%), and 3 dietary ratios of SID Ile-Val:Lys (68-77, 78-87, and 88-97%). Performance parameters were assessed from 1 to 35 days of age.

View Article and Find Full Text PDF

miR-18a-5p/PXR/SREBP2 Was Involved in MAFLD Associated With Methyl Tert-Butyl Ether Among Petrol Station Workers.

Liver Int

February 2025

Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, China.

Background: Metabolic associated fatty liver disease (MAFLD), previously defined as non-alcoholic fatty liver disease (NAFLD), has been shown to be closely related to many environmental pollutants. Lately, we found methyl tert-butyl ether (MTBE), a new environmental pollutant, could increase NAFLD risk in American adults, which still needs more population epidemiological studies to verify, and its pathogenic mechanism is not yet clear.

Methods: We conducted a cross-sectional study among petrol station workers, diagnosed their MAFLD according to internationally recognised diagnostic criteria, assessed the potential association of MTBE exposure with MAFLD risk, and explored the miR-18a-5p/PXR/SREBP2 pathway as possible pathogenic mechanisms in male Wistar rats and HepaRG cells treated with MTBE.

View Article and Find Full Text PDF

Epigenetics in Neurodegenerative Diseases.

Subcell Biochem

January 2025

Faculty of Medicine and Faculty of Life Sciences, Institute of Biomedical Sciences (ICB), Universidad Andres Bello, Santiago, Chile.

Healthy brain functioning requires a continuous fine-tuning of gene expression, involving changes in the epigenetic landscape and 3D chromatin organization. Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) are three multifactorial neurodegenerative diseases (NDDs) that are partially explained by genetics (gene mutations and genetic risk factors) and influenced by non-genetic factors (i.e.

View Article and Find Full Text PDF

Context: Statin treatment lowers low-density lipoprotein (LDL) cholesterol thereby reducing cardiovascular risk. Meta-analyses of clinical trials report a higher risk of new-onset type 2 diabetes with statins. Current clinical evidence regarding effects of statins on insulin sensitivity and beta-cell function is limited.

View Article and Find Full Text PDF

Introduction: Type 2 diabetes (T2D) is a prevalent metabolic disorder linked to chronic inflammation and endothelial dysfunction, which contributes to the development of microvascular complications (MVCs) such as diabetic retinopathy (DR) and diabetic neuropathy (DN). Genetic factors, including variations in the ABO gene, may influence these complications. This study aimed to investigate the association between the ABO rs2073823 polymorphism and the risk of MVCs in patients with T2D, as well as its impact on inflammatory biomarkers, endothelial markers, and lipid profiles.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!