Targeting of Integrin-Linked Kinase with a Small Interfering RNA Inhibits Endothelial Cell Migration, Proliferation and Tube Formation in vitro

Guo, Lili; Yu, Wenzhen; Li, Xiaoxin; Zhao, Gang; He, Ping‐an

doi:10.1159/000232971

Cited by 9 publications

(14 citation statements)

References 61 publications

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“…The migration was suppressed by disrupting the F-actin assembly. 36 Our study confirmed that the ILK/AKT pathway was possibly involved in wound contraction by regulating wound fibroblast migration. ILK-mediated regulation of migration may be related to fibronectin.…”

Section: Ilk-pi3k/akt Pathway and Wound Contraction G LI Et Alsupporting

confidence: 76%

ILK–PI3K/AKT pathway participates in cutaneous wound contraction by regulating fibroblast migration and differentiation to myofibroblast

Sun

et al. 2016

Laboratory Investigation

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The interactions between fibroblasts and the extracellular matrix in wound contraction are mainly mediated via integrin signaling. Integrin-linked kinase (ILK) is a key mediator in integrin signal transduction. We investigated the role of ILK in cutaneous wound contraction. We found that ILK was involved in cutaneous wound healing in rats, and ILK and PI3K/AKT inhibitors inhibited wound contraction and re-epithelialization, consequently delaying wound healing in vivo. Further, using in vitro studies, we demonstrated that ILK and PI3K/AKT inhibitors suppressed the contraction of fibroblastpopulated collagen lattices, inhibited fibroblast migration, and interrupted the effect of TGF-β 1 on promoting alpha smooth muscle actin (α-SMA) expression in fibroblasts. When ILK expression was directly blocked by ILK small interfering RNA transfection, the migration and α-SMA expression of normal dermal fibroblasts were significantly suppressed as well. The data suggest that the ILK-PI3K/AKT signaling pathway mediates cutaneous wound contraction by regulating fibroblast migration and differentiation to myofibroblasts.

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Section: Ilk-pi3k/akt Pathway and Wound Contraction G LI Et Alsupporting

confidence: 76%

ILK–PI3K/AKT pathway participates in cutaneous wound contraction by regulating fibroblast migration and differentiation to myofibroblast

Sun

et al. 2016

Laboratory Investigation

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“…21,34,35 ILK also has a critical role in cardiac development and function, particularly as a component of the cardiac stretch sensor. 36 However, little is known about the postnatal physiological role of ILK in relation to NO synthesis and vascular function.…”

Section: Discussionmentioning

confidence: 99%

Integrin-Linked Kinase Regulates Vasomotor Function by Preventing Endothelial Nitric Oxide Synthase Uncoupling

Herránz

Marquez

Guijarro

et al. 2012

Circulation Research

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Results: ILK expression was detected in the endothelial cell layer of nonatherosclerotic vessels but was absent from the endothelium of atherosclerotic arteries. Live ultrasound imaging revealed that acetylcholine-mediated vasodilatation was impaired in cKO mice. These mice exhibited lowered agonist-induced nitric oxide synthase (NOS) activity and decreased cyclic guanosine monophosphate and nitrite production. ILK deletion caused endothelial NOS (eNOS) uncoupling, reflected in reduced tetrahydrobiopterin (BH4) levels, increased BH2 levels, decreased dihydrofolate reductase expression, and increased eNOS-dependent generation of superoxide accompanied by extensive vascular protein nitration. ILK reexpression prevented eNOS uncoupling in cKO cells, whereas superoxide formation was unaffected by ILK depletion in eNOS-KO cells, indicating eNOS as a primary source of superoxide anion. eNOS and ILK coimmunoprecipitated in aortic lysates from control animals, and eNOS-ILK-shock protein 90 interaction was detected in human normal mammary arteries but was absent from human atherosclerotic carotid arteries. eNOS-ILK interaction in endothelial cells was prevented by geldanamycin, suggesting heat shock protein 90 as a binding partner. Key Words: atherosclerosis Ⅲ oxidative stress Ⅲ uncoupling protein E ndothelial dysfunction is defined as impaired endothelium-dependent relaxation of blood vessels in response to the endogenous vasodilator nitric oxide (NO). Endothelial dysfunction is concomitant with changes in vascular structure associated with many forms of vascular disease, such as hypertension and atherosclerosis. 1 Atherosclerotic lesions develop mostly in areas exposed to disturbed blood flow, whereas endothelial cells exposed to laminar flow are protected against inflammatory activation and show higher relative expression of endothelial NO synthase (eNOS) and superoxide dismutase. 2,3 Most NO in the vasculature is produced by eNOS, with a minor contribution from neuronal-type nNOS expressed in vascular smooth muscle cells. Under inflammatory conditions, vascular cells can express iNOS, which produces large amounts of NO and contributes further to vascular damage. 4 eNOS can be activated by hemodynamic forces, autacoids, hormones, and growth factors. NO relaxes vessels via activation of soluble guanylyl cyclase (sGC). The resulting elevated levels of cyclic guanosine monophosphate (cGMP) activate cGMP-dependent protein kinase type I (cGKI), which phosphorylates downstream targets that regulate the Original received July 29, 2011; revision received December 13, 2011; accepted December 14, 2011. In November 2011 actin-myosin cytoskeleton and the calcium clearing mechanism, leading to vasorelaxation. 5 Many endothelial cell molecules, including integrins, sense shear stress. 6,7 Integrin-linked kinase (ILK), a key regulator of blood vessel integrity, is a phosphoinositide 3-kinasedependent serine/threonine kinase that binds to the cytoplasmic domain of ß-integrin and lies upstream of many intracellular signaling pa...

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“…It is well known that VEGF is the most critical growth factor for angiogenesis, and it plays a key role in EC biology. Guo et al (2009) observed that silencing ILK with siRNA significantly reduced VEGF secretion in the culture medium of RF/6A cells. So, the observed phenotype in pDNA-ILK EPCs prompted us to investigate the expression of VEGF using western blot and ELISA.…”

mentioning

confidence: 92%

Ultrasound Microbubble-Mediated Delivery of Integrin-Linked Kinase Gene Improves Endothelial Progenitor Cells Dysfunction in Pre-Eclampsia

Cui

Yan²,

Luo³

et al. 2014

DNA and Cell Biology

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Pre-eclampsia (PE) is a specific vascular complication in pregnancy whose precise mechanism is still unclear. We hypothesized that endothelial progenitor cells (EPCs), the precursor of endothelial cells, might be impaired in patients with PE and hold a great promise for the treatment of PE. In the present study, we analyzed the EPCs number and expression of integrin-linked kinase (ILK) in PE patients. We confirmed that both EPCs number and ILK expression were diminished in PE patients. Next, we transfected EPCs with ILK gene using ultrasonic microbubble technique (UMT) for the first time, as UMT is a novel type of gene transfer technology showing promising applications in stem cells apart from EPCs. To further investigate the transfection efficiency of UMT, RT-PCR analysis and western blot were used to examine the messenger RNA (mRNA) and protein level of ILK. After transfection of the ILK gene, EPCs function was tested to illustrate the role of ILK in cell proliferation, apoptosis, migration, and secretion. The results of the in vitro study suggested that UMT, a novel gene delivery system, could be considered a potent physical method for EPCs transfection. Moreover, the growth and angiogenetic properties of EPCs are enhanced by introducing ILK. This study may afford a new trend for EPCs transfection and gene therapy in PE.

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Targeting of Integrin-Linked Kinase with a Small Interfering RNA Inhibits Endothelial Cell Migration, Proliferation and Tube Formation in vitro

Cited by 9 publications

References 61 publications

ILK–PI3K/AKT pathway participates in cutaneous wound contraction by regulating fibroblast migration and differentiation to myofibroblast

ILK–PI3K/AKT pathway participates in cutaneous wound contraction by regulating fibroblast migration and differentiation to myofibroblast

Integrin-Linked Kinase Regulates Vasomotor Function by Preventing Endothelial Nitric Oxide Synthase Uncoupling

Ultrasound Microbubble-Mediated Delivery of Integrin-Linked Kinase Gene Improves Endothelial Progenitor Cells Dysfunction in Pre-Eclampsia

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