Dermal mesenchymal stem cells promote angiogenesis in HMEC-1 via activation of the angiopoietin 1/Tie2 pathway in psoriasis

Background: Abnormal proliferation of microvessels in the superficial dermis is a key pathological feature of psoriasis. The angiopoietin 1 (Ang1)/Tie2 axis regulates angiogenesis and is closely associated with the cellular microenvironment. Our previous studies demonstrated that dermal mesenchymal stem cells (DMSCs) derived from psoriatic lesions can promote angiogenesis in human umbilical vein endothelial cells; however, the link between this proangiogenic effect and the Ang1/Tie2 axis remains unclear.

Objective: To investigate the potential role of Ang1 in DMSC-mediated promotion of angiogenesis in human dermal microvascular endothelial cells (HMEC-1) in the context of psoriasis.

Methods: DMSCs were isolated from the skin of 18 psoriatic patients and 18 healthy individuals. Normal DMSCs (N-DMSCs) with ANGPT1 overexpression and psoriatic DMSCs (P-DMSCs) with ANGPT1 knockdown were co-cultured with HMEC-1, respectively. qRT-PCR and Western blotting were used to detect the expression levels of Ang1, Tie2, and other related genes. CCK-8, EdU staining, Transwell chamber, and Matrigel tube formation assays were employed to evaluate HMEC-1 function. A psoriasis mouse model was established using IMQ, and HE staining was performed to measure the epidermal thickness of lesional skin.

Results: Compared with N-DMSCs, P-DMSCs exhibited significantly higher mRNA and protein expression levels of Ang1. Co-culture of HMEC-1 with ANGPT1-overexpressing N-DMSCs increased the phosphorylation level of Tie2 in HMEC-1, along with enhanced cell proliferation, migration, tube formation, and upregulated expression of angiogenesis-related genes. These proangiogenic effects were attenuated following the addition of a PI3K inhibitor. In contrast, co-culture with ANGPT1-knockdown P-DMSCs inhibited HMEC-1 function, and this inhibitory effect could be reversed by treatment with a PI3K activator. Additionally, ANGPT1 overexpression exacerbated psoriatic symptoms in IMQ-induced mice, while ANGPT1 knockdown alleviated these symptoms.

Conclusion: P-DMSCs promote the proliferation, migration, and tube formation of HMEC-1 by upregulating Ang1, which activates Tie2 and the downstream PI3K/AKT pathway. These findings provide a theoretical basis for understanding the mechanism of abnormal angiogenesis in psoriasis and support the development of targeted therapies for this disease.