| Autor: |
Renaud L; Department of Medicine, Rheumatology, Medical University of South Carolina, Charleston, SC 29425, USA., Waldrep KM; Department of Medicine, Rheumatology, Medical University of South Carolina, Charleston, SC 29425, USA., da Silveira WA; Department of Biological Sciences, School of Life Sciences and Education, Staffordshire University, Stoke-on-Trent ST4 2DF, UK., Pilewski JM; Department of Medicine, Pulmonary, University of Pittsburgh, Pittsburgh, PA 15213, USA., Feghali-Bostwick CA; Department of Medicine, Rheumatology, Medical University of South Carolina, Charleston, SC 29425, USA. |
| Abstrakt: |
Systemic sclerosis (SSc) is a connective tissue disorder that results in fibrosis of the skin and visceral organs. SSc-associated pulmonary fibrosis (SSc-PF) is the leading cause of death amongst SSc patients. Racial disparity is noted in SSc as African Americans (AA) have a higher frequency and severity of disease than European Americans (EA). Using RNAseq, we determined differentially expressed genes (DEGs; q < 0.1, log2FC > |0.6|) in primary pulmonary fibroblasts from SSc lungs (SScL) and normal lungs (NL) of AA and EA patients to characterize the unique transcriptomic signatures of AA-NL and AA-SScL fibroblasts using systems-level analysis. We identified 69 DEGs in "AA-NL vs. EA-NL" and 384 DEGs in "AA-SScL vs. EA-SScL" analyses, and a comparison of disease mechanisms revealed that only 7.5% of DEGs were commonly deregulated in AA and EA patients. Surprisingly, we also identified an SSc-like signature in AA-NL fibroblasts. Our data highlight differences in disease mechanisms between AA and EA SScL fibroblasts and suggest that AA-NL fibroblasts are in a "pre-fibrosis" state, poised to respond to potential fibrotic triggers. The DEGs and pathways identified in our study provide a wealth of novel targets to better understand disease mechanisms leading to racial disparity in SSc-PF and develop more effective and personalized therapies. |
