Integrin-linked kinase controls retinal angiogenesis and is linked to Wnt signaling and exudative vitreoretinopathy

Park, Hongryeol; Yamamoto, Hiroyuki; Mohn, Lucas; Ambühl, Lea Maria Margareta; Kanai, Kenichi; Schmidt, Inga; Kim, Kee-Pyo; Fraccaroli, Alessia; Feil, Silke; Junge, Harald J.; Montañez, Eloi; Berger, Wolfgang; Adams, Ralf H.

doi:10.1038/s41467-019-13220-3

Cited by 64 publications

(61 citation statements)

References 69 publications

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“…According to recent literatures, ILK can promote the proangiogenic activity of MSCs via their paracrine effect [ 33 , 34 ]. Thus, the proangiogenic ability of ILK gene-modified BMSCs was evaluated in vitro and in vivo.…”

Section: Resultsmentioning

confidence: 99%

Therapeutic effect of integrin-linked kinase gene-modified bone marrow-derived mesenchymal stem cells for streptozotocin-induced diabetic cystopathy in a rat model

et al. 2020

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Background: Diabetic cystopathy (DCP) is a chronic complication of diabetes mainly within the submucosal and muscular layers of the bladder due to the hyperglycemia-induced ischemia. As no effective therapies are currently available, the administration of optimized mesenchymal stem cells (MSCs) provides a potential treatment of DCP. Thus far, new strategy, such as genetic modification of MSCs, has been developed and has shown promising outcomes of various disorders. Methods: This study was conducted using integrin-linked kinase (ILK) gene-modified bone marrow-derived stem cells (BMSCs) for streptozotocin (STZ)-induced diabetic cystopathy in a rat model. In total, 68 male Sprague-Dawley rats were randomized into five groups: sham control (control group, n = 10); DCP model alone (DM group, n = 10); DCP rats intravenously treated with BMSCs (BMSC group, n = 16); DCP rats accepted adenoviral vector-infected BMSCs (Ad-null-BMSC group, n = 16) and DCP rats accepted ILK adenoviral vector-infected BMSCs (Ad-ILK-BMSC group, n = 16). Diabetic rats accepted cell transplantation in the experimental group (2 rats per group) were sacrificed for the bladder tissue on the third day, 7th day, and 14th day of treatment respectively ahead of schedule. At 4 weeks after treatment, all rats in five groups accepted urodynamic studies to evaluate bladder function and were sacrificed for bladder tissue. Results: Our data showed that the underactive bladder function was significantly improved in DCP rats intravenously treated with ILK gene-modified BMSCs compared to those in the DM, BMSCs, and Ad-null-BMSC group. Meanwhile, we found that gene-modified BMSC treatment significantly promoted the activation of the AKT/ GSK-3β pathway by increasing phosphorylation and led to the enhancement of survival. In addition, the expression levels of angiogenesis-related protein vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and stromal cell-derived factor-1 (SDF-1) were significantly higher in the Ad-ILK-BMSC group than that in the DM, BMSCs, and Ad-null-BMSC group as assessed by enzyme-linked immunosorbent assay and western blot. As two indicators of vascular endothelial cell markers, the expression of von Willebrand factor (vWF) and CD31 by

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Section: Resultsmentioning

confidence: 99%

Therapeutic effect of integrin-linked kinase gene-modified bone marrow-derived mesenchymal stem cells for streptozotocin-induced diabetic cystopathy in a rat model

et al. 2020

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“…Phosphorylation at Ser552 induces β-catenin accumulation in the nucleus and increases its transcriptional activity [ 59 , 60 , 61 ]. The specificities of these antibodies were validated as recognizing the appropriate epitopes in various model systems, including knockout animals and cell lines [ 57 , 61 , 62 , 63 , 64 , 65 ]. IHC staining for both activated (β-catenin pS552 ) and membrane β-catenin revealed dynamic staining patterns that are spatially and temporally regulated during embryonic gestation.…”

Section: Resultsmentioning

confidence: 99%

Dynamic Expression Profiles of β-Catenin during Murine Cardiac Valve Development

Guo

Glover

Risner

et al. 2020

JCDD

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β-catenin has been widely studied in many animal and organ systems across evolution, and gain or loss of function has been linked to a number of human diseases. Yet fundamental knowledge regarding its protein expression and localization remains poorly described. Thus, we sought to define whether there was a temporal and cell-specific regulation of β-catenin activities that correlate with distinct cardiac morphological events. Our findings indicate that activated nuclear β-catenin is primarily evident early in gestation. As development proceeds, nuclear β-catenin is down-regulated and becomes restricted to the membrane in a subset of cardiac progenitor cells. After birth, little β-catenin is detected in the heart. The co-expression of β-catenin with its main transcriptional co-factor, Lef1, revealed that Lef1 and β-catenin expression domains do not extensively overlap in the cardiac valves. These data indicate mutually exclusive roles for Lef1 and β-catenin in most cardiac cell types during development. Additionally, these data indicate diverse functions for β-catenin within the nucleus and membrane depending on cell type and gestational timing. Cardiovascular studies should take into careful consideration both nuclear and membrane β-catenin functions and their potential contributions to cardiac development and disease.

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“…ILK is known to bind to α-pv and PINCH to form the IPP-complex, which critically controls integrin signaling at focal complexes and focal adhesions (Legate et al, 2006;Wickstrom et al, 2010). ILK is essential for vessel development and vessel homeostasis (Friedrich et al, 2004;Tan et al, 2004;Park et al, 2019). Moreover, ILK regulates cell-cell junctions in epithelial cells (Vespa et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Among the proteins that were precipitated with Coro1B we identified known Coro1B binding partners such as subunits of the Arp2/3 complex and cofilin as well as the novel interactor ILK (Figure 4A and Supplementary Table S1 in the Data Supplement) (Howell et al, 2015). Given that ILK has also been identified as a key regulator of EC function and blood vessel homeostasis, we further characterized the Coro1B-ILK interaction (Friedrich et al, 2004;Park et al, 2019). Consistently with the proteomic data, endogenous ILK was co-immunoprecipitated with Coro1B-GFP ( Figure 4B).…”

Section: Coro1b Interacts With Ilk and Colocalizes With α-Pv In Ecsmentioning

confidence: 99%

Coronin 1B Controls Endothelial Actin Dynamics at Cell–Cell Junctions and Is Required for Endothelial Network Assembly

Werner¹,

Weckbach²,

Salvermoser³

et al. 2020

Front. Cell Dev. Biol.

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Development and homeostasis of blood vessels critically depend on the regulation of endothelial cell-cell junctions. VE-cadherin (VEcad)-based cell-cell junctions are connected to the actin cytoskeleton and regulated by actin-binding proteins. Coronin 1B (Coro1B) is an actin binding protein that controls actin networks at classical lamellipodia. The role of Coro1B in endothelial cells (ECs) is not fully understood and investigated in this study. Here, we demonstrate that Coro1B is a novel component and regulator of cell-cell junctions in ECs. Immunofluorescence studies show that Coro1B colocalizes with VEcad at cell-cell junctions in monolayers of ECs. Live-cell imaging reveals that Coro1B is recruited to, and operated at actin-driven membrane protrusions at cellcell junctions. Coro1B is recruited to cell-cell junctions via a mechanism that requires the relaxation of the actomyosin cytoskeleton. By analyzing the Coro1B interactome, we identify integrin-linked kinase (ILK) as new Coro1B-associated protein. Coro1B colocalizes with α-parvin, an interactor of ILK, at the leading edge of lamellipodia protrusions. Functional experiments reveal that depletion of Coro1B causes defects in the actin cytoskeleton and cell-cell junctions. Finally, in matrigel tube network assays, depletion of Coro1B results in reduced network complexity, tube number and tube length. Together, our findings point toward a critical role for Coro1B in the dynamic remodeling of endothelial cell-cell junctions and the assembly of endothelial networks.

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Integrin-linked kinase controls retinal angiogenesis and is linked to Wnt signaling and exudative vitreoretinopathy

Cited by 64 publications

References 69 publications

Therapeutic effect of integrin-linked kinase gene-modified bone marrow-derived mesenchymal stem cells for streptozotocin-induced diabetic cystopathy in a rat model

Therapeutic effect of integrin-linked kinase gene-modified bone marrow-derived mesenchymal stem cells for streptozotocin-induced diabetic cystopathy in a rat model

Dynamic Expression Profiles of β-Catenin during Murine Cardiac Valve Development

Coronin 1B Controls Endothelial Actin Dynamics at Cell–Cell Junctions and Is Required for Endothelial Network Assembly

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