Increased expression of uPA, uPAR, and PAI-1 in psoriatic skin and in basal cell carcinomas

Abstract

There is substantial evidence implicating the urokinase system in tissue remodeling during neo-vascularization, inflammation, tumor invasion, and metastasis. Regulated degradation of the extracellular matrix at the leading edge of migrating cells, mediated by uPA and uPAR, is required for tissue remodeling, invasiveness, and angiogenesis. Psoriasis and basal cell carcinoma (BCC) are the most common skin diseases. Pathogenesis of both of them is associated with keratinocyte hyperproliferation, inflammatory cell migration, and angiogenesis-processes in which the plasminogen system (uPA, uPAR, tPA, and PAI-1) plays a crucial role. In the present study, the comparative analysis of uPA, uPAR, tPA, and PAI-1 expression in the normal skin, in the biopsies of patients with psoriasis vulgaris, and BCC was carried out. uPA, uPAR, and PAI-1 expression was up-regulated in the epidermis of psoriatic skin and in tumor cells in BCC. Increased uPAR expression was detected in the derma of psoriatic lesions and in the stroma surrounding tumor cells in BCC. Increased expression of uPA in epidermal cells in psoriasis and in tumor cells in BCC suggests an important role of the uPA system for aggressively proliferating and invading cells of epidermal origin. A possible activation of the stroma, as a result of uPA-uPAR interaction between tumor cells and the surrounding stroma, is suggested.

SuPAR, an emerging biomarker in kidney and inflammatory diseases

“…SuPAR was highly expressed in the dermis of patients with psoriasis, yet its serum levels failed to correlate with disease severity. Nonetheless, suPAR’s value needs to be better studied in patients with various stages of psoriasis to confirm these findings 45. SLE is another dermatological autoinflammatory disease, characterised by systemic inflammation that involves nearly all the vital organs.…”

“…The serine protease activity of plasmin has been found to be involved in inflammatory reactions, tissue remodelling and degradation of matrix proteins in several immune-mediated dermatological and rheumatological diseases 45. Such conditions are characterised by multifactorial pathways leading to systemic inflammation with end-organ damage.…”

Reduced humidity induces skin barrier dysfunction and secretion of dipeptidyl peptidase-4 (DPP-4) in a skin-equivalent model

“…The conditioned medium from an epidermal model cultured at low humidity enhanced MMP-1 secretion by normal human dermal fibroblasts [7]. DPP4, EMMPRIN, GDF-15, HGF, uPAR, MIP-3α, ST2 and leptin, which were regulated at reduced humidity in our experiment, are known to have functions in skin remodeling and inflammation [18][19][20][21][22][23][24].…”

Enhanced Wound Healing- and Inflammasome-Associated Gene Expression in TNFAIP3-Interacting Protein 1- (TNIP1-) Deficient HaCaT Keratinocytes Parallels Reduced Reepithelialization

“…In addition to their expression changes associated with wound repair [63], the cohort of SERPINE (plasminogen activator inhibitor 1), PLAUR (plasminogen activator, urokinase receptor), and PLAU (plasminogen activator, urokinase) are upregulated in psoriasis compared to amounts beneath the limits of detection or at very low levels in healthy epidermis [64]. As compared to HaCaT keratinocytes with usual levels of TNIP1 protein under poly (I:C) conditions, TNIP1-deficient cells exposed to this DAMP/PAMP had increased expression of each of the following: SERPINE, 9-fold; PLAUR,~3-fold; and PLAU,~2-fold.…”