Knockdown of the KINDLIN-2 Gene and Reduced Expression of Kindlin-2 Affects Vascular Permeability in Angiogenesis in a Mouse Model of Wound Healing

Abstract

BackgroundAngiogenesis is an important component of wound healing and tissue repair. Kindlin-2 is an integrin-associated protein, encoded by the KINDLIN-2 gene, which has been shown to affect cell adhesion and migration of cells, including endothelial cells. The aim of this study was to use a mouse model of wound healing to evaluate the effects of expression of KINDLIN-2 on angiogenesis in wound healing in vivo.Material/MethodsThirty-six male C57BL/6 mice were studied in an established model that used a wound created on the back. Mice were divided randomly into three groups: the normal group (n=12) received injections of normal (0.9%) saline; the KINDLIN-2(−) group (n=12) received injections of adeno-associated virus with small interfering (si)RNA targeting the KINDLIN-2 gene (AAV-KINDLIN-2-siRNA); and the control (group (n=12) received injections of adeno-associated virus containing a scrambled RNA sequence (AAV-control-RNA). Wound healing was analyzed by biochemical examination of the exudates and histology. Evans blue dye was injected into the caudal vein of each mouse, two weeks after wound healing to assess neovascular permeability.ResultsWound healing was significantly delayed in the KINDLIN-2 gene knockdown mice (AAV-KINDLIN-2-siRNA) compared with that of the normal group and the control group, and neovascular permeability was increased. In the AAV-KINDLIN-2-siRNA group, blood vessels were shorter and thinner compared with the normal group and the control group.ConclusionsIn a mouse model of wound healing, KINDLIN-2 gene knockdown inhibited wound healing, and increased neovascular permeability in vivo.

Elevated kindlin-2 promotes tumour progression and angiogenesis through the mTOR/VEGFA pathway in melanoma

“…Our previous study showed that kindlin-2 affects neovascular permeability [20], and here, we detected whether its expression in melanoma cells had an effect on angiogenesis. We found that kindlin-2 overexpression in melanoma cells promoted vascular formation and that the downregulation of kindlin-2 inhibited vascular formation (Figure 3A).…”

“…Previously, we indicated that neovascular permeability was increased and blood vessels were shorter and thinner in kindlin-2 gene knockdown mice [20]. Liao et al [24] showed that kindlin-2 is necessary for angiogenic sprouting in vitro and for tumour angiogenic development in vivo .…”

The Genomes of Two Billfishes Provide Insights into the Evolution of Endothermy in Teleosts

“…Previous work suggested that kindlin-2 interacts with endothelial adherens junctions to support vascular barrier integrity ( Pluskota et al. 2017 ) and a knockdown of this gene increases neovascular permeability ( Ying et al. 2018 ).…”

Involvement of kindlin‐2 in irisin’s protection against ischaemia reperfusion‐induced liver injury in high‐fat diet‐fed mice

“…Kindlin‐2 has been shown to promote tumour invasion and metastasis 54,55 . It is also essential for preserving integrity of the heart, vascular permeability in angiogenesis, chondrogenesis, regulation of podocyte structure and function, control of adipogenesis and lipid metabolism as well as bone homeostasis 56‐61 . Kindlins protect cells against oxidative damage 62‐65 .…”