Slit2 Promotes Angiogenic Activity Via the Robo1-VEGFR2-ERK1/2 Pathway in Both In Vivo and In Vitro Studies

Abstract

Slit2 overexpression promoted angiogenic effects in both a laser-induced CNV mouse model and HUVECs and promoted the biological activity of endothelial cells. Slit2 may promote angiogenesis by upregulating Robo1 and activating the VEGFR2-ERK1/2 pathway.

Slit2/Robo4 axis may contribute to endothelial cell dysfunction and angiogenesis disturbance in systemic sclerosis

“…In fact, when we interfered with Slit2/Robo4 signalling, SSc-MVECs exhibited a significant improvement in their ability to proliferate, migrate and form capillary-like structures in vitro. In endothelial cells, Slit2/Robo4 axis was found to prevent the activation of MAP kinases,16 Arf small GTPases21 or Src family kinase (SFK)18 mediated by proangiogenic factors such as VEGF 45. In this context, we observed that treatment of H-MVECs with Slit2 reduced p-Src to levels comparable with those of basal SSc-MVECs, suggesting that this secreted glycoprotein may suppress angiogenesis through the inhibition of SFK signalling pathways.…”

Photoreceptor Cell–Derived CAPN5 Regulates Retinal Pigment Epithelium Cell Proliferation Through Direct Regulation of SLIT2 Cleavage

“…The SLIT2/ROBO pathway has been associated with retinal neovascularization, proliferative diabetic retinopathy, and RPE cells, 31,32 as well as adipose-secreted SLIT2-C fragments that regulate thermogenesis and metabolic function of brown and beige fat. 24 The secreted SLIT2 and SLIT2-N fragments promoted retinal neovascularization in the developing retina and abnormal pathologies in diabetic retinopathy.…”

Enhanced VEGF signalling mediates cerebral neovascularisation via downregulation of guidance protein ROBO4 in a rat model of diabetes

“…First, we focused on ROBO4 and did not address the role of Slit2–ROBO1 signalling, which has been shown to be pro-angiogenic [45]. Second, the in vivo overexpression approach is not specific for endothelial cells.…”