Potential treatment of keloid pathogenesis with follistatin 288 by blocking the activin molecular pathway
| Autor: | Peter Temple-Smith, Seungmin Ham, Craig A. Harrison, Graeme Southwick, David M. de Kretser, Euan M. Wallace |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
endocrine system Follistatin medicine.medical_treatment Connective tissue Gene Expression Dermatology Biochemistry 030207 dermatology & venereal diseases 03 medical and health sciences Retinoids 0302 clinical medicine Keloid Downregulation and upregulation Gene expression Plasminogen Activator Inhibitor 1 medicine Humans skin and connective tissue diseases Molecular Biology Cells Cultured Inhibin-beta Subunits integumentary system biology Chemistry Interleukin-6 Growth factor Connective Tissue Growth Factor Fibroblasts medicine.disease Elastin Up-Regulation CTGF 030104 developmental biology medicine.anatomical_structure embryonic structures Cancer research biology.protein Wound healing hormones hormone substitutes and hormone antagonists |
| Zdroj: | Experimental dermatologyREFERENCES. 30(3) |
| ISSN: | 1600-0625 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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