Mucopolysaccharide polysulfate promotes microvascular stabilization and barrier integrity of dermal microvascular endothelial cells via activation of the angiopoietin-1/Tie2 pathway

Abstract

Background: Mucopolysaccharide polysulfate (MPS) is a heparinoid and MPS-containing formulations are widely used as moisturizers for dry skin and to treat peripheral vascular insufficiency. Although MPS has therapeutic effects in skin diseases with microvascular abnormalities, the effects of MPS on microvascular function remain incompletely understood. Objective: The aim of this study was to evaluate the functional activities of MPS on human pericytes (HPC) and human dermal microvascular endothelial cells (HDMEC) in vitro, and on microvascular permeability of the skin. Methods: The protein expression of angiopoietin (Ang)-1 in HPC, and platelet-derived growth factor-BB (PDGF-BB) and phosphorylated tyrosine-protein kinase receptor 2 (Tie2) in HDMEC were measured in the presence or absence of MPS. The vascular barrier was evaluated by the expressions of claudin-5 and vascular endothelial (VE)-cadherin, and transendothelial electrical resistance (TEER). Results: In HPC, MPS dose-dependently enhanced Ang-1 secretion, which activated Tie2 in HDMEC. In HDMEC, MPS significantly increased the production of PDGF-BB, which is important for the recruitment of HPC to the vascular endothelium, and significantly increased the phosphorylation of Tie2, which results in the activation of the Ang-1/Tie2 signaling . MPS significantly increased the expression of tight junction protein claudin-5 and TEER in the HDMEC. Moreover, the intradermal injection of MPS prevented vascular endothelial growth factor-induced increase in vascular permeability in mouse skin. Conclusion:We found that MPS promoted microvascular stabilization and barrier integrity in HDMEC via Ang-1/Tie2 activation. These results suggest that MPS might improve microvascular abnormalities in various diseases accompanied by disturbances in Ang-1/Tie2 signaling.

Angiopoietin-1 promotes triple-negative breast cancer cell proliferation by upregulating carboxypeptidase A4

“…The perivascular cells of mature blood vessels express ANG1, which plays an essential role in the development and stabilization of blood vessels [ 32 , 33 ], and ANG1 has more recently been reported to be expressed in various tumor cells, such as breast cancer, gastric cancer and hepatocellular carcinoma. Accumulating evidence suggests that ANG1 is associated with tumor progression [ 34 – 36 ] and poor survival [37] because it exhibits distinct correlations with cancer-associated fibroblasts [ 38 , 39 ], endothelial cells [40] , and the tumor microenvironment [ 34 , 41 , 42 ].…”

Increased Angiopoietin-1 and -2 levels in human vitreous are associated with proliferative diabetic retinopathy

“…Compared to controls, vitreous samples of PDR patients revealed an up-regulation of all analyzed angiogenic factors (Fig 1 and Table 3). The mean level of VEGF-A in vitreous samples of Angiopoietin-2 R&D Systems DANG20 undiluted [27] CCL3/MIP-1α R&D Systems DMA00 1:50 [28] Galectin-1 R&D Systems DGAL10 1:20 [29] IFN-γ Invitrogen BMS228 undiluted [12] IL-1β/IL-1F2 R&D Systems DLB50 undiluted [12] IL-8/CXCL8 R&D Systems D8000C undiluted [30] TNF-α R&D Systems DTA00D undiluted [31] PIGF R&D Systems DPG00 undiluted [12] VEGF-A Invitrogen BMS277-2 undiluted [12,32] https://doi.org/10.1371/journal.pone.0280488.t001…”

Efficacy and safety of 1565‐nm nonablative fractional laser combined with mucopolysaccharide polysulfate cream for erythematous acne scars

“…Second, MPS cream could repair the damaged skin tissue in acne scars by promoting dermal microcirculation, anticoagulation, and normal connective tissue regeneration action 11,13,16. MPS cream can contribute to dermal microvascular stabilization and barrier integrity 28,29. Finally, MPS cream might improve the appearance of acne scars by promoting epidermal F I G U R E 3 The mean quantitative GSS score change of each side evaluated from baseline to after treatment.…”