First Characterization of the Transcriptome of Lung Fibroblasts of SSc Patients and Healthy Donors of African Ancestry

Renaud, Ludivine, Waldrep, Kristy M., da Silveira, Willian A., Pilewski, Joseph M. and Feghali-Bostwick, Carol A. (2023) First Characterization of the Transcriptome of Lung Fibroblasts of SSc Patients and Healthy Donors of African Ancestry. International Journal of Molecular Sciences, 24 (4). p. 3645. ISSN 1422-0067

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Abstract or description

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.

Item Type:	Article
Uncontrolled Keywords:	systemic sclerosis; scleroderma; pulmonary fibrosis; racial disparity; functional enrichment; pathway analysis
Faculty:	School of Life Sciences and Education > Biological and Biomedical Sciences
Depositing User:	Willian DA SILVEIRA
Date Deposited:	22 Apr 2024 12:27
Last Modified:	22 Apr 2024 12:27
URI:	https://eprints.staffs.ac.uk/id/eprint/8215

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