Your browser doesn't support javascript.
loading
The Soluble Guanylate Cyclase Stimulator BAY 41-2272 Attenuates Transforming Growth Factor ß1-Induced Myofibroblast Differentiation of Human Corneal Keratocytes.
Rosa, Irene; Fioretto, Bianca Saveria; Romano, Eloisa; Buzzi, Matilde; Mencucci, Rita; Marini, Mirca; Manetti, Mirko.
Afiliação
  • Rosa I; Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
  • Fioretto BS; Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
  • Romano E; Section of Internal Medicine, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
  • Buzzi M; Section of Internal Medicine, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
  • Mencucci R; Eye Clinic, Careggi Hospital, Department of Neurosciences, Psychology, Pharmacology and Child Health (NEUROFARBA), University of Florence, 50134 Florence, Italy.
  • Marini M; Eye Clinic, Careggi Hospital, Department of Neurosciences, Psychology, Pharmacology and Child Health (NEUROFARBA), University of Florence, 50134 Florence, Italy.
  • Manetti M; Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
Int J Mol Sci ; 23(23)2022 Dec 05.
Article em En | MEDLINE | ID: mdl-36499651
Corneal transparency, necessary for vision and depending on the high organization of stromal extracellular matrix, is maintained by keratocytes. Severe or continuous corneal injuries determine exaggerated healing responses resulting in the formation of irreversible fibrotic scars and vision impairment. Soluble guanylate cyclase (sGC) stimulation demonstrated antifibrotic effects in both experimental fibrosis and human lung and skin fibroblasts. Here, we assessed whether sGC stimulation with BAY 41-2272 could attenuate transforming growth factor ß1 (TGFß1)-induced myofibroblast differentiation of human corneal keratocytes. Cells were challenged with TGFß1, with/without BAY 41-2272 preincubation, and subsequently assessed for viability, proliferation, migration, chemoinvasion, as well for the expression of myofibroblast/fibroblast activation markers and contractile abilities. Treatment with BAY 41-2272 did not affect keratocyte viability, while preincubation of cells with the sGC stimulator was able to inhibit TGFß1-induced proliferation, wound healing capacity, and invasiveness. BAY 41-2272 was also able to attenuate TGFß1-induced myofibroblast-like profibrotic phenotype of keratocytes, as demonstrated by the significant decrease in ACTA2, COL1A1, COL1A2, FN1 and PDPN gene expression, as well as in α-smooth muscle actin, α-1 chain of type I collagen, podoplanin, vimentin and N-cadherin protein expression. Finally, BAY 41-2272 significantly counteracted the TGFß1-induced myofibroblast-like ability of keratocytes to contract collagen gels, reduced phosphorylated Smad3 protein levels, and attenuated gene expression of proinflammatory cytokines. Collectively, our data show for the first time that BAY 41-2272 is effective in counteracting keratocyte-to-myofibroblast transition, thus providing the rationale for the development of sGC stimulators as novel promising modulators of corneal scarring and fibrosis.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ceratócitos da Córnea / Lesões da Córnea Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ceratócitos da Córnea / Lesões da Córnea Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article