BackgroundTo 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|
PERRUCCI, GIANLUCA LORENZO (Primo) (Corresponding)
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|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1186/s12967-018-1730-1|
|Appare nelle tipologie:||01 - Articolo su periodico|