Objective: Systemic sclerosis (SSc) is a fibrotic disease attributed to both genetic susceptibility and environmental factors. This study was undertaken to investigate the associations between SSc-associated genetic variants and the expression of extracellular matrix (ECM) genes in human fibroblasts stimulated with silica particles in time-course and dose-response experiments.
Methods: A total of 200 fibroblast strains were examined for ECM gene expression after stimulation with silica particles. The fibroblasts were genetically profiled using Immunochip assays and then subjected to whole-genome genotype imputation. Associations of genotypes and gene expression were first analyzed in a Caucasian cohort and then validated in a meta-analysis combining the results from Caucasian, African American, and Hispanic subjects. A linear mixed model for longitudinal data analysis was used to identify genetic variants associated with the expression of ECM genes, and the associations were validated by using a haplotype-based longitudinal association test on regions that included the loci identified.
Results: The single-nucleotide polymorphism rs58905141 in TNFAIP3 was consistently associated with time-course and/or dose-response expression of MMP3 and MMP1 in the fibroblasts stimulated with silica particles in both the analysis of Caucasian subjects only and the meta-analysis. Results of the haplotype-based analysis validated the association signals.
Conclusion: Our findings indicate that a genetic variant of TNFAIP3 is strongly associated with the silica-induced profibrotic response of fibroblasts. In silico functional analysis based on the ENCODE database revealed that rs58905141 might affect the binding activities of the transcription factors for TNFAIP3. This is the first genome-wide study of interactions between genetic and environmental factors in a complex SSc fibroblast model.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767670 | PMC |
| http://dx.doi.org/10.1002/art.39476 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Hydrophobic PU fabric with synergistic conductive networks for boosted high sensitivity, wide linear-range wearable strain sensor.
Nanotechnology
January 2025
Anhui Agricultural University, Hefei, 230036, P. R. China, Hefei, 230036, CHINA.
Strain sensing fabrics are able to sense the deformation of the outside world, bringing more accurate and real-time monitoring and feedback to users. However, due to the lack of clear sensing mechanism for high sensitivity and high linearity carbon matrix composites, the preparation of high performance strain sensing fabric weaving is still a major challenge. Here, an elastic polyurethane(PU)-based conductive fabric(GCPU) with high sensitivity, high linearity and good hydrophobicity is prepared by a novel synergistic conductive network strategy.
View Article and Find Full Text PDFPolydopamine-Mediated, Centrifugal Force-Driven Gold Nanoparticle-Deposited Microneedle SERS Sensors for Food Safety Monitoring Theoretical Study of the SERS Substrate Fabrication.
ACS Sens
January 2025
The Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Municipal Education Committee Key Laboratory of Molecular Imaging Probes and Sensors, and Department of Chemistry, Shanghai Normal University, Shanghai 200234, P. R. China.
Microneedle (MN) sensors have great promise for food safety detection, but the rapid preparation of MNs for surface-enhanced Raman scattering (SERS) sensors with tunable and homogeneous nanoparticles remains a great challenge. To address this, a SERS sensor of gold nanoparticles@polydopamine@poly(methyl methacrylate) MN (AuNPs@PDA@PMMA-MN) was developed. The extended-Derjaguin-Landau-Verwey-Overbeek theory was applied to calculate the interaction energy between AuNPs and PDA.
View Article and Find Full Text PDFDecoupling evolution of water footprint of energy and its driving factors: Evidence from Northeast China.
PLoS One
January 2025
School of Economics and Management, Northeastern Petroleum University, Daqing, China.
Energy and water are interlinked and inseparable resources of vital importance to the survival and development of human society. Exploring the relationship between energy and water is of great practical significance for the sustainable development of resources. The uneven regional distribution of energy and water in China has exacerbated energy-related water shortages.
View Article and Find Full Text PDFHigh-resolution national radon maps based on massive indoor measurements in the United States.
Proc Natl Acad Sci U S A
January 2025
Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA 02114.
Radon, a common radioactive indoor air pollutant, is the second leading cause of lung cancer in the United States. Knowledge about its distribution is essential for risk assessment and designing efficient protective regulations. However, the three current radon maps for the United States are unable to provide the up-to-date, high-resolution, and time-varying radon concentrations.
View Article and Find Full Text PDFClassification and spatial characteristics of different development stages in China: Evidence from the contribution rate of production factors.
PLoS One
January 2025
Real Estate Research Center, Nanjing Agricultural University, Nanjing, China.
This paper aims to reveal the changing characteristics of the contribution rates of different production factors in China since the reform and opening up from two dimensions: stage and space. The study used national data from 1978 to 2021 and provincial data from 2000 to 2020, combined with methods such as C-D production function and spatial econometrics for analysis. Research has found that: (1) In terms of stage characteristics, during the structural adjustment stage (1978-1998), economic growth mainly relies on capital and labor input, and the contribution rate of land factors gradually decreases.
View Article and Find Full Text PDFWant 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!