Premium
Potential treatment of keloid pathogenesis with follistatin 288 by blocking the activin molecular pathway
Author(s) -
Ham Seungmin,
Harrison Craig,
de Kretser David,
Wallace Euan M.,
Southwick Graeme,
TempleSmith Peter
Publication year - 2021
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.14223
Subject(s) - follistatin , keloid , ctgf , fibroblast , connective tissue , endocrinology , wound healing , medicine , transforming growth factor , cancer research , gene expression , growth factor , cell culture , biology , pathology , gene , immunology , receptor , genetics
Keloids are benign tumours caused by abnormal wound healing driven by increased expression of cytokines, including activin A. This study compared effects of activins on normal and keloid‐derived human dermal fibroblasts and investigated a novel treatment for keloids using follistatin. Normal skin and keloid tissue samples from 11 patients were used to develop primary fibroblast cultures, which were compared in terms of their histology and relevant gene (qRT‐PCR and RNAseq) and protein (ELISA) expression. Activin A ( INHBA ) and connective tissue growth factor ( CTGF ) gene expression were significantly upregulated in keloid fibroblasts, as was activin A protein expression in cell lysates and culture medium. Activator protein 1 inhibitor (SR11302) significantly decreased INHBA and CTGF expression in keloid fibroblasts and a single treatment of follistatin over 5 days significantly inhibited activin and various matrix‐related genes in keloid fibroblasts when compared to controls. Follistatin, by binding activin A, suppressed CTGF expression suggesting a novel therapeutic role in managing keloids and perhaps other fibrotic diseases.