Contribution of Endothelial Laminin-Binding Integrins to Cellular Processes Associated with Angiogenesis

Abstract

Endothelial cells engage extracellular matrix and basement membrane components through integrin-mediated adhesion to promote angiogenesis. Angiogenesis involves the sprouting of endothelial cells from pre-existing vessels, their migration into surrounding tissue, the upregulation of angiogenesis-associated genes, and the formation of new endothelial tubes. To determine whether the endothelial laminin-binding integrins, α6β4, and α3β1 contribute to these processes, we employed RNAi technology in organotypic angiogenesis assays, as well in migration assays, in vitro. The endothelial depletion of either α6β4 or α3β1 inhibited endothelial sprouting, indicating that these integrins have non-redundant roles in this process. Interestingly, these phenotypes were accompanied by overlapping and distinct changes in the expression of angiogenesis-associated genes. Lastly, depletion of α6β4, but not α3β1, inhibited migration. Taken together, these results suggest that laminin-binding integrins regulate processes associated with angiogenesis by distinct and overlapping mechanisms.

Integrin expression and extracellular matrix adhesion of septoclasts, pericytes, and endothelial cells at the chondro‐osseous junction and the metaphysis of the proximal tibia in young mice

“…The absence of the BM at the outer surface of pericytes at the metaphysis is presumably attributed to angiogenesis related to osteogenesis. Integrins α2 and α6 at the cell membrane of endothelial cells participate in the adhesion between endothelial cells and the wrapping BM (Adorno‐Cruz & Liu, 2019; Languino et al, 1989; Mezu‐Ndubuisi & Maheshwari, 2021; Xu & LaFlamme, 2022; Yazlovitskaya et al, 2019). We showed the corresponding expression of integrin α2/α6 and laminin at the COJ; however, some endothelial cells at the COJ showed faint immunoreactivity against integrin α6 (Figure 7), indicating partial degradation and/or absence of the BM, as shown by immunolocalization of collagen IV and laminin (Figures 9 and 10).…”

Fibrosis quantification using multiphoton excitation imaging of picrosirius red stained cardiac tissue

“…FLIM imaging in this red wavelength range is still not very common due to limitations of the current GaAsP detectors. For spectral imaging, the most commonly used systems that are commercially available have a full range of 410 nm to 696 nm 37 . Hyperspectral imaging will be even better when commercial instruments allow for zooming in on the red part of the spectrum.…”

Mechanisms of vascular invasion after cartilage injury and potential engineering cartilage treatment strategies

“…During vascular formation, integrins can simultaneously bind both MMPs and ECM, promoting endothelial cell secretion and MMP activation, which can degrade ECM components and release VEGF , thus facilitating endothelial cell migration 68 . Additionally, integrins synergistically interact with angiogenic growth factors, promoting endothelial cell proliferation 69,70 . During cartilage injury, integrins act as the main participants in the binding of chondrocytes to the ECM and can upregulate the expression of MMP‐13 , leading to changes in collagen type, decreased stability, and ultimately cartilage damage, forming the pathological basis of OA 71,72 .…”

“…68 Additionally, integrins synergistically interact with angiogenic growth factors, promoting endothelial cell proliferation. 69,70 During cartilage injury, integrins act as the main participants in the binding of chondrocytes to the ECM and can upregulate the expression of MMP-13, leading to changes in collagen type, decreased stability, and ultimately cartilage damage, forming the pathological basis of OA. 71,72 Chondrocytes from patients with OA show high expression of the β1 subunit and all α subtypes of integrins, which correlates with the severity of cartilage injury.…”