Abstract
BackgroundThis study aimed to assessed whether Talin-1 is involved in the pathogenesis of aortic dissection via regulating vascular smooth muscle cell (VSMC) biological function.MethodsHuman aortic samples were obtained from organ donors who died from nonvascular diseases as normal controls and from patients undergoing surgical repair of thoracic aortic dissection. The expression level and distribution of Talin-1 were detected using westernblot analysis and immunohistochemistry in each sample. We inhibited the expression of Talin-1 via RNA interference in VSMCs. VSMC proliferation was detected by Cell-counting Kit-8 analyses. Scratch test and flow cytometry were used to identify the migration and apoptosis ability. Antibody microarray analysis and qRT-PCR were used to detect some protein and mRNA changes which were induced by Talin-1 downregulation.ResultsTalin-1 was significantly downregulated in the media of aortic dissection samples compared with controls (P < 0.05). Talin-1 knockdown significantly induced VSMC proliferation and migration in vitro. Proteins which involved in cell cycle can be regulated by downregulating Talin-1. Down regulation of Talin-1 can significanly increased the expression of anaphase-promoting complex subunit 2 (APC2) and decreased p19 alternative reading frame (p19ARF), Cullin-3, and beta actin’s expression.ConclusionsTalin-1 induces VSMCs proliferation and migration. It downregulated in aortic dissection, which might play a potential role in the development of aortic dissection.
Highlights
This study aimed to assessed whether Talin-1 is involved in the pathogenesis of aortic dissection via regulating vascular smooth muscle cell (VSMC) biological function
Differential expression of Talin-1 protein in aortic dissection versus normal aorta tissue specimens To reveal the expression features of Talin-1 in human aorta, we use western bot analysis to detect the expression of Talin-1 in Aortic dissection (AD) and their matched NA tissues (Fig. 1a)
Talin-1 was decreased in the AD tissues compared with the NA tissues (P
Summary
This study aimed to assessed whether Talin-1 is involved in the pathogenesis of aortic dissection via regulating vascular smooth muscle cell (VSMC) biological function. Pathological vascular remodeling plays a key role in AD [2, 3]. As the major cell in aortic media, the functional change of vascular smooth muscle. Talin-1 located at the adhesion complex between cells and their extracellular matrix (ECM) and it regulates integrin and focal adhesion signaling [10, 11]. Major insights into the function of Talin-1 were derived from experiments demonstrating that the Talin-1 head binds the cytoplasmic tails of β integrin subunits, leading to the final step in “inside-out” integrin activation [12, 13]
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