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EnglishBackgroundTo date the TGF-1 activation mediated by integrin 5 during fibrosis is well-known. This process has been shown also in the heart, where cardiac fibroblasts (CF) differentiate into -smooth muscle actin (-SMA)-positive myofibroblasts (MyoFB). Here, we studied the effects on CF, isolated by spontaneously hypertensive rats (SHR), of integrin 5 inhibition in MyoFB differentiation.MethodsStaining and immunohistochemistry were performed on rat cardiac tissue. CF were isolated by enzymatic digestion from SHR (SHR-CF) and normotensive WKY (WKY-CF) rat hearts and then treated for in vitro evaluation.ResultsSHR heart tissues revealed a higher TGF-1 expression vs. WKY samples. SHR-CF showed an enhanced SMAD2/3 activation and an up-regulated expression of -SMA, a typical MyoFB marker, especially after TGF-1 treatment. Immunostaining on cardiac tissues revealed a higher expression of integrin 5 in SHR vs. WKY rat hearts. In vitro results confirmed the up-regulation of integrin 5 expression in SHR-CF at basal condition and after TGF-1 treatment, in comparison with WKY-CF. Inhibition of integrin 5 by cilengitide treatment led a decreased expression of 5, collagen I, and -SMA in SHR-CF vs. WKY-CF, resulting in a diminished differentiation of CF into MyoFB. Taking together, results suggested that SHR-CF are more susceptible to TGF-1, showing an up-regulated activation of SMAD2/3 signaling, and an increased 5, -SMA, and collagen I expression. Hypertension stimulus promoted an up-regulation of integrin 5 on SHR cardiac tissue and its in vitro inhibition reverted pro-fibrotic events of SHR-CF.ConclusionInhibition of integrin 5 exerted by cilengitide strongly diminished SHR-CF differentiation into detrimental MyoFB. So, integrin 5 might be considered a novel therapeutic target and cilengitide an effective pharmacological tool to limit the progression of hypertension-induced cardiac fibrosis.
Integrin ανβ5 in vitro inhibition limits pro-fibrotic response in cardiac fibroblasts of spontaneously hypertensive rats / G.L. Perrucci, V.A. Barbagallo, M. Corlianò, D. Tosi, R. Santoro, P. Nigro, P. Poggio, G. Bulfamante, F. Lombardi, G. Pompilio. - In: JOURNAL OF TRANSLATIONAL MEDICINE. - ISSN 1479-5876. - 16:1(2018 Dec 12).
| Titolo: | Integrin ανβ5 in vitro inhibition limits pro-fibrotic response in cardiac fibroblasts of spontaneously hypertensive rats |
| Autori: | BARBAGALLO, VERONICA ANTONIETTA (Secondo) LOMBARDI, FEDERICO (Penultimo) POMPILIO, GIULIO (Ultimo) |
| Parole Chiave: | Cilengitide; Hypertension; Integrin ανβ5; Myofibroblast; TGF-β1 |
| Settore Scientifico Disciplinare: | Settore BIO/11 - Biologia Molecolare Settore MED/08 - Anatomia Patologica Settore MED/23 - Chirurgia Cardiaca |
| Data di pubblicazione: | 12-dic-2018 |
| Rivista: | |
| Tipologia: | Article (author) |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1186/s12967-018-1730-1 |
| Appare nelle tipologie: | 01 - Articolo su periodico |
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| Perrucci-integrin12967_2018_Article_1730.pdf | Publisher's version/PDF | Open Access Visualizza/Apri |
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