Semaphorin 3A potentiates the profibrotic effects of transforming growth factor-β1 in the cornea
| Autor: | Keith Nehrke, Krystel R. Huxlin, Kye-Im Jeon |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Stromal cell Biophysics Biochemistry Article Transforming Growth Factor beta1 03 medical and health sciences 0302 clinical medicine Semaphorin Fibrosis Cornea medicine Animals Myofibroblasts Molecular Biology Cells Cultured Wound Healing business.industry Cell Differentiation Drug Synergism Semaphorin-3A SEMA3A Cell Biology Fibroblasts medicine.disease Cell biology 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cats sense organs Wound healing business Myofibroblast Corneal Injuries Transforming growth factor |
| Zdroj: | Biochem Biophys Res Commun |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2019.10.107 |
| Popis: | Corneal scarring is a major cause of blindness worldwide with few effective therapeutic options. Finding a treatment would be of tremendous public health benefit, but requires a thorough understanding of the complex interactions that underlie this phenomenon. Here, we tested the hypothesis that the large increase in expression of Semaphorin 3A (SEMA3A) in corneal wounds contributes to the development of stromal fibrosis. We first verified this increased expression in vivo, in a cat model of photorefractive keratectomy-induced corneal wounding. We then examined the impact of adding exogenous SEMA3A to cultured corneal fibroblasts, and assessed how this affected the ability of transforming growth factor-beta1 (TGF-β1) to induce their differentiation into myofibroblasts. Finally, we examined how siRNA knockdown of endogenous SEMA3A affected these same phenomena. We found exogenous SEMA3A to significantly potentiate TGF-β1’s profibrotic effects, with only a minimal contribution from cell-intrinsic SEMA3A. Our results suggest a previously unrecognized interaction between SEMA3A and TGF-β1 in the wounded cornea, and a possible contribution of SEMA3A to the regulation of tissue fibrosis and remodeling in this transparent organ. |
| Databáze: | OpenAIRE |
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