Plasminogen Binding and Activation at the Mesothelial Cell Surface Promotes Invasion through a Collagen Matrix.

Plasminogen (Plg) activation to the serine protease plasmin (Pla) plays a key role in regulating wound healing and fibrotic responses, particularly when bound to cell surface receptors. Our previous work suggested that mesothelial cells bind Plg at the cell surface, though no Plg receptors were described for these cells. Since mesothelial cells contribute to injury responses, including cellular differentiation to a mesenchymal-like phenotype and extracellular matrix remodeling, we hypothesized that Plg binding would promote these responses. Here, we confirm that Plg binds to both pleural and peritoneal mesothelial cells via the lysine-binding domain present in Plg, and we demonstrate the presence of three Plg receptors on the mesothelial cell surface: α-Enolase, Annexin A2, and Plg-RKT. We further show that bound-Plg is activated to Pla on the cell surface and that activation is blocked by an inhibitor of urokinase plasminogen activator or by the presence of animal-derived FBS. Lastly, we demonstrate that Plg promotes mesothelial cell invasion through a type I collagen matrix but does not promote cellular differentiation or proliferation. These data demonstrate for the first time that mesothelial cells bind and activate Plg at the cell surface and that active Pla is involved in mesothelial cell invasion without cell differentiation.

Guide to tinted sunscreens in skin of color.

Disorders of hyperpigmentation, such as melasma and post-inflammatory hyperpigmentation, disproportionately affect skin of color and have a profound impact on quality of life. Exposure to ultraviolet light (UVL) is a well-documented factor in these disorders. However, recent studies show that visible light (VL) is a significant and underrecognized contributor to hyperpigmentation, especially in skin of color. Our objective is to review the role of VL in disorders of hyperpigmentation and that of tinted sunscreens in protecting against VL. Tinted sunscreens containing iron oxides should be recommended over nontinted sunscreens for patients prone to disorders of hyperpigmentation, as iron oxides protect against VL in addition to UVL. Tinted sunscreens are more effective than nontinted sunscreens in preventing melasma relapses and reducing hyperpigmentation, and they may also enhance the depigmenting efficacy of topical hydroquinone. In the search for an ideal tinted sunscreen for a particular patient, several factors must be considered, including a broad spectrum with adequate coverage of both UVL and VL, tint, formulation texture, active ingredients, and cost. VL is increasingly recognized as a major contributor of hyperpigmentation, and adequate treatment for disorders of hyperpigmentation should include protection against VL. Tinted sunscreens are ideal but require consideration of cosmesis, efficacy, and affordability.