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Modulation of microvascular smooth muscle adhesion and mechanotransduction by integrin-linked kinase.

ABSTRACT: In this study, we investigated the involvement of integrin-linked kinase (ILK) in the adhesion of arteriolar vascular smooth muscle cells (VSMC) to fibronectin (FN) and in the mechano-responsiveness of VSMC focal adhesions (FA).ILK was visualized in VSMC by expressing EGFP-ILK and it was knocked down using ILK-shRNA constructs. Atomic force microscopy (AFM) was used to characterize VSMC interactions with FN, VSMC stiffness and to apply and measure forces at a VSMC single FA site.ILK was localized to FA and silencing ILK promoted cell spreading, enhanced cell adhesion, reduced cell proliferation and reduced downstream phosphorylation of GSK-3beta and PKB/Akt. AFM studies demonstrated that silencing ILK enhanced alpha5beta1 integrin adhesion to FN and enhanced VSMC contraction in response to a pulling force applied at the level of a single FN-FA site.ILK functions in arteriolar VSMC appear linked to multiple signaling pathways and processes that inhibit cell spreading, cell adhesion, FA formation, adhesion to FN and the mechano-responsiveness of FN-FA sites.

SUBMITTER: Huang S

PROVIDER: S-EPMC2923833 | biostudies-other | 2010 Feb

REPOSITORIES: biostudies-other

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Modulation of microvascular smooth muscle adhesion and mechanotransduction by integrin-linked kinase.

Huang Shaoxing S Sun Zhe Z Li Zhaohui Z Martinez-Lemus Luis A LA Meininger Gerald A GA

Microcirculation (New York, N.Y. : 1994) 20100201 2

<h4>Objective</h4>In this study, we investigated the involvement of integrin-linked kinase (ILK) in the adhesion of arteriolar vascular smooth muscle cells (VSMC) to fibronectin (FN) and in the mechano-responsiveness of VSMC focal adhesions (FA).<h4>Methods</h4>ILK was visualized in VSMC by expressing EGFP-ILK and it was knocked down using ILK-shRNA constructs. Atomic force microscopy (AFM) was used to characterize VSMC interactions with FN, VSMC stiffness and to apply and measure forces at a VS ...[more]

PMID: 20163538

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Project description:Background and purposeRecombinant osteopontin (rOPN) has been reported to be neuroprotective in stroke animal models. The purpose of this study is to investigate a potential role and mechanism of nasal administration of rOPN on preserving the vascular smooth muscle phenotype in early brain injury after subarachnoid hemorrhage (SAH).MethodsOne hundred and ninety-two male adult Sprague-Dawley rats were used. The SAH model was induced by endovascular perforation. Integrin-linked kinase small interfering RNA was intracerebroventricularly injected 48 hours before SAH. The integrin receptor antagonist fibronectin-derived peptide Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP), focal adhesion kinase inhibitor Fib-14, and Rac-1 inhibitor NSC23766 were administered 1 hour before SAH induction. rOPN was administered via the intracerebroventricular and nasal route after SAH. SAH grade, neurological scores, brain water content, brain swelling, hematoxylin and eosin staining, India ink angiography, Western blots, and immunofluorescence were used to study the mechanisms of rOPN on the vascular smooth muscle phenotypic transformation.ResultsThe marker proteins of vascular smooth muscle phenotypic transformation α-smooth muscle actin decreased and embryonic smooth muscle myosin heavy chain (SMemb) increased significantly at 24 and 72 hours in the cerebral arteries after SAH. rOPN prevented the changes of α-smooth muscle actin and SMemb and significantly alleviated neurobehavioral dysfunction, increased the cross-sectional area and the lumen diameter of the cerebral arteries, reduced the brain water content and brain swelling, and improved the wall thickness of cerebral arteries. These effects of rOPN were abolished by GRGDSP, integrin-linked kinase small interfering RNA, and NSC23766. Intranasal application of rOPN at 3 hours after SAH also reduced neurological deficits.ConclusionsrOPN prevented the vascular smooth muscle phenotypic transformation and improved the neurological outcome, which was possibly mediated by the integrin receptor/integrin-linked kinase/Rac-1 pathway.

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Modulation of microvascular smooth muscle adhesion and mechanotransduction by integrin-linked kinase.

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Modulation of microvascular smooth muscle adhesion and mechanotransduction by integrin-linked kinase.

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