Esomeprazole Inhibits Proliferation of Scleroderma Fibroblasts via Cell Cycle Regulation

Authors

• Mohammad A Khan
• Shaheer Koniyan
• Manisha Ahir
• Anil G Jegga
• Maureen D Mayes
• David Gius
• Justin Leung
• Mark D Bonnen
• Sydney B Montesi
• Yohannes T Ghebre

Language

English

Publication Date

1-1-2025

Journal

Frontiers in Pharmacology

DOI

10.3389/fphar.2025.1703115

PMID

41567630

PMCID

PMC12816232

PubMedCentral® Posted Date

1-6-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Scleroderma is a complex autoimmune disease characterized by abnormal fibroblast proliferation and excessive collagen deposits in the skin and internal organs. We previously showed that esomeprazole, an FDA-approved drug for gastric disorders, may prevent dermal fibrosis.

Methods: To test this, we evaluated the antiproliferative effect of esomeprazole and the underlying molecular mechanisms using primary fibroblasts derived from patients with scleroderma. BrdU incorporation, flow cytometry, immunofluorescence, Western blot analysis, RNA sequencing, and functional enrichment analysis were performed.

Results: Esomeprazole inhibited the proliferation of scleroderma fibroblasts in a dose-dependent manner, as measured by BrdU incorporation and Ki-67 marker. Intriguingly, esomeprazole arrested fibroblasts in the G1 phase of the cell cycle, resulting in a reduction of cells in the S phase. Expression of p21, a known inhibitor of cyclin-dependent kinases (CDKs), was elevated, while CDK1 and CDK2 levels were decreased following esomeprazole treatment.

Discussion: These results suggest that esomeprazole induces G1 phase arrest by upregulating p21 and downregulating CDK1 and CDK2, thereby inhibiting fibroblast proliferation. These data provide important insights into how esomeprazole regulates fibroblast proliferation in scleroderma and suggest that it may represent a potential therapeutic intervention.

Keywords

esomeprazole, fibroblast, proliferation, scleroderma, CDKs, skin fibrosis

Published Open-Access

yes

Recommended Citation

Khan, Mohammad A; Koniyan, Shaheer; Ahir, Manisha; et al., "Esomeprazole Inhibits Proliferation of Scleroderma Fibroblasts via Cell Cycle Regulation" (2025). Faculty, Staff and Student Publications. 3650.
https://digitalcommons.library.tmc.edu/uthmed_docs/3650