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Integrin ???5 in vitro inhibition limits pro-fibrotic response in cardiac fibroblasts of spontaneously hypertensive rats.
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ABSTRACT: Background
To 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.Methods
Staining 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.Results
SHR 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.Conclusion
Inhibition 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.
SUBMITTER: Perrucci GL
PROVIDER: S-EPMC6292173 | biostudies-literature | 2018 Dec
REPOSITORIES: biostudies-literature
Publications
Integrin ανβ5 in vitro inhibition limits pro-fibrotic response in cardiac fibroblasts of spontaneously hypertensive rats.
Journal of translational medicine 20181212 1
<h4>Background</h4>To date the TGF-β1 activation mediated by integrin ανβ5 during fibrosis is well-known. This process has been shown also in the heart, where cardiac fibroblasts (CF) differentiate into α-smooth muscle actin (α-SMA)-positive myofibroblasts (MyoFB). Here, we studied the effects on CF, isolated by spontaneously hypertensive rats (SHR), of integrin ανβ5 inhibition in MyoFB differentiation.<h4>Methods</h4>Staining and immunohistochemistry were performed on rat cardiac tissue. CF wer ...[more]
