Melanocyte pigmentation inversely correlates with MCP‐1 production and angiogenesis‐inducing potential

Abstract

The incidence of certain angiogenesis-dependent diseases is higher in Caucasians than in African Americans. Angiogenesis is amplified in wound healing and cornea models in albino C57 mice compared with black C57 mice. Moreover, mouse and human melanocytes with low pigmentation stimulate endothelial cell (EC) proliferation and migration in vitro more than melanocytes with high pigmentation. This effect is due, in part, to the secretion of an angiogenic protein called fibromodulin (FMOD) from lowly pigmented melanocytes. Herein, we expand upon the mechanism contributing to increased angiogenesis in lighter skin and report that monocyte chemotactic protein-1 (MCP-1) is secreted by nonpigmented mouse melanocytes by 5- to 10-fold more than pigmented melanocytes. MCP-1 protein stimulates EC proliferation and migration in vitro and angiogenesis in vivo. Mechanistic studies determine that FMOD is upstream of MCP-1 and promotes its secretion from both melanocytes and activated ECs via stimulation of NF-κB activity. Mice injected with FMOD-neutralizing antibodies show 2.3-fold decreased levels of circulating MCP-1. Human studies confirmed that, on average, Caucasians have 2-fold higher serum levels of MCP-1 than African Americans. Taken together, this study implicates the FMOD/MCP-1 pathway in the regulation of angiogenesis by local melanocytes and suggests that melanogenic activity may protect against aberrant angiogenic diseases.

Proteoglycan form and function: A comprehensive nomenclature of proteoglycans

“…Finally, recent reports have shown that fibromodulin promotes in vitro and in vivo angiogenesis [ 492 ], and this is particularly prominent in melanocyte-secreted fibromodulin [ 493 ]. Mechanistically, fibromodulin appears to be secreted at high levels in low pigmented melanocytes and it stimulates the secretion of monocyte chemotactic protein-1, which is a powerful angiogenic factor [ 494 ].…”

Conditioned medium from primary cytotrophoblasts, primary placenta-derived mesenchymal stem cells, or placental tissue promoted HUVECs angiogenesis in vitro

“…CXCL5 is also part of the CXC chemokine family and controls angiogenic properties by enhancing microvascular endothelial cell migration and tube formation [32]. Monocyte chemotactic protein-1 (MCP-1) (also called chemokine (C-C motif) ligand 2, CCL2) upregulates FGF, PDGF, and VEGF expression, stimulates EC proliferation and migration, and induces MMP-1 secretion by ECs to degrade the ECM [65]. In addition to these ve proangiogenic factors, the expression of three traditional proangiogenic factors in placental tissue was also increased.…”

Differential expression of inflammatory cytokines and chemokines in lipopolysaccharide‐stimulated melanocytes from lightly and darkly pigmented skin

“…Moreover, it stimulates proliferation and migration of endothelial cells and may contribute to the mechanism of increased pathological angiogenesis in lighter skin. Adini et al demonstrated that CCL2 was highly upregulated in nonpigmented mouse melanocytes compared to the pigmented cells. It was also shown that Caucasians have 2‐fold higher serum levels of CCL2 protein than African Americans.…”