ITGA9 Inhibits Proliferation and Migration of Dermal Microvascular Endothelial Cells in Psoriasis.

Background: Cell proliferation, migration, and angiogenesis are aberrant in psoriatic human dermal microvascular endothelial cells (HDMECs), resulting in abnormal endothelial function and microvascular dilation in psoriasis. Objective: To explore the role of Integrin subunit alpha 9 (ITGA9) in proliferation and migration of dermal microvascular endothelial cells. Methods: HDMECs were isolated from the skin of 6 psoriatic patients and 6 healthy controls. Expression levels of ITGA9 mRNA and protein were assessed with qRT-PCR and Western blot, respectively, while miqRT-PCR was used to determine expression levels of miR-146a-3p. Cell proliferation and migration were assessed in human microvascular endothelial cell line (HMEC-1), following overexpression of either ITGA9 or miR-146a-3p, or co-transfection with miR-146a-3p-mimic and pLVX - ITGA9. Cell viability was detected by Cell Counting Kit-8 assay and 5-ethynyl-2'-deoxyuridine (EdU) cell proliferation assay. Cell apoptosis was assessed, using annexin V-FITC/PI apoptosis detection kit, while cell migration was detected by wound healing and transwell assay. Results: Expression levels of ITGA9 were significantly decreased in psoriatic HDMECs compared to normal controls. Moreover, expression levels of miR-146a-3p were higher in psoriatic HDMECs than in normal controls. Overexpression of miR-146a-3p lowered expression levels of ITGA9, accompanied by increased proliferation and migration of HMEC-1 in vitro. In contrast, overexpression of ITGA9 inhibited proliferation and migration of HMEC-1, while increasing expression levels of cdc42, ki67, focal adhesion kinase (FAK), c-Src tyrosine kinase (Src), RAC1 and RhoA. Conclusion: ITGA9 can repress the proliferation and migration of HMEC-1, suggesting utility of ITGA9 as a potential therapeutic intervention for psoriasis.