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.; Feghali-Bostwick, Carol A.

doi:10.3390/ijms24043645

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.; Feghali-Bostwick, Carol A.

Authors

Ludivine Renaud

Kristy M. Waldrep

Dr Willian Da Silveira W.A.DaSilveira@salford.ac.uk
Lecturer

Joseph M. Pilewski

Carol A. Feghali-Bostwick

Abstract

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.

Citation

Renaud, L., Waldrep, K. M., da Silveira, W. A., Pilewski, J. M., & Feghali-Bostwick, C. A. (in press). First Characterization of the Transcriptome of Lung Fibroblasts of SSc Patients and Healthy Donors of African Ancestry. International Journal of Molecular Sciences, 24(4), 3645. https://doi.org/10.3390/ijms24043645

Journal Article Type	Article
Acceptance Date	Feb 1, 2023
Online Publication Date	Feb 11, 2023
Deposit Date	Oct 25, 2024
Publicly Available Date	Oct 28, 2024
Journal	International Journal of Molecular Sciences
Print ISSN	1661-6596
Electronic ISSN	1422-0067
Publisher	MDPI
Peer Reviewed	Peer Reviewed
Volume	24
Issue	4
Pages	3645
DOI	https://doi.org/10.3390/ijms24043645