Targeting p300 HAT domain with inhibitor A-485 to treat fibrosis in systemic sclerosis fibroblasts (in-vitro) – UROP Spring Symposium 2024

Targeting p300 HAT domain with inhibitor A-485 to treat fibrosis in systemic sclerosis fibroblasts (in-vitro)

Sonia Ling

Pronouns: she/her

Research Mentor(s): Swati Bhattacharyya
Research Mentor School/College/Department: Internal Medicine, Rheumatology / Medicine
Program:
Authors: Swati Bhattacharyya, Sonia Ling
Session: Session 7: 4:40 pm – 5:30 pm
Poster: 10

Abstract

Scleroderma, or systemic sclerosis (SSc), is a rare and chronic disease that mostly affects women from ages 30 to 50. Patients with SSc experience chronic hardening in their skin and connective tissues, and tend to have symptoms that include joint pain, exaggerated response to cold, and heartburn. The disease is associated with fibrosis, a condition that causes build-up of scar tissue in the skin and has no currently available therapies. However, it is known that the transforming growth factor-ß (TGF-ß) cytokine governs persistent fibroblast activation and, by extension, fibrosis. Past research has also indicated that the histone-acetyltransferase (HAT) domain of transcriptional coactivator p300 stimulates TGF-ß induced fibrotic responses. Therefore, to investigate novel approaches for alleviating fibrosis, our research project tested the effect of A-485—a highly selective p300 HAT inhibitor—on TGF-ß induced normal fibroblasts and patient-derived SSc fibroblasts. We used various approaches to measure fibrotic changes, such as RT-qPCR, western blotting, and immunofluorescent staining. Our results ultimately found that A-485 potently reduced the TGF-ß induced fibrotic phenotype and constitutive SSc phenotype within SSc patients.

Biomedical Sciences, Interdisciplinary, Natural/Life Sciences

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