The Integrative Studies of Genetic and Environmental Factors in Systemic Sclerosis
Abstract
During this first year of the project, we established 60 primary fibroblast strains from normal controls and SSc patients who have been genotyped with HLA markers. We performed stimulation assays with silica and/or carbon, titanium particles in 60 primary fibroblast strains. Our results showed that both silica and carbon particle can activate fibroblasts toward fibrotic changes. To develop a comprehensive statistical analysis in study of dynamic properties of fibroblasts, we employed widely used state-space equations in systems science to model biological systems, and used expectation-maximization (EM) algorithms and Kalman filter to estimate the parameters in the models. We applied the developed state-space models and performed dynamic analysis of gene expression of partial TGF beta pathway in both normal and SSc fibroblasts stimulated by silica. In comparing fibroblasts from SSc patients and normal controls, we demonstrated that SSc fibroblasts are unstable and less controllable in response to silica stimulation, which may contribute to susceptibility of SSc fibroblasts to fibrotic changes. Next step, we will identify which genetic components inside SSc patients contribute to these changes and to susceptibility to environmental stimuli. Therefore, our studies are fulfilled with original proposal in the grant.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2008
- Accession Number
- ADA486215
Entities
People
- Xiaodong Zhou
Organizations
- University of Texas Health Science Center at Houston