The role of UV-induced cutaneous matrix metalloproteinases and mi-RNAs in the pathogenesis of lupus erythematosus

Cutaneous (CLE) and systemic lupus erythematosus (SLE) are autoimmune diseases with a multifactorial pathogenesis. Ultraviolet radiation (UVR) is the most important trigger of CLE; however, the degree of photosensitivity varies between the clinical subtypes. The expression of matrix metalloproteinases (MMPs)—important enzymes involved in skin turnover and homeostasis—is modulated by UVR.

To investigate the causality of the clinically observed effects of UVR, sun-exposed lesional skin samples from patients with different subtypes of lupus erythematosus (LE) were examined by immunohistochemistry for the expression of MMP1 and MMP28 and compared with biopsies from polymorphous light eruption (PLE) and healthy skin (HS). The expression of micro-RNAs (miR-31 and miR-150)—regulators of MMP expression and cellular metabolism—in the samples was determined by in-situ hybridization and correlated with the expression of the glucose transporter 1 (GLUT1) receptor to examine potential metabolic regulation. To assess potential UVR regulation of MMP28, we performed in vitro experiments in healthy keratinocytes and fibroblasts.

MMP28 expression was differentially affected by UVA1 and UVB irradiation in keratinocytes and fibroblasts. Compared with all other LE subtypes, as well as PLE and HS samples, MMP28 expression in Chilblain LE skin showed a distinct vertical distribution, reaching as far as the upper layers of the dermis. This vertical expression pattern coincided with decreased GLUT1 levels and with increased expression of miR-31 and miR-150 in the epidermis of patients with Chilblain LE. These data provide evidence for a potential metabolic dysregulation that may play a role in the etiology of LE. Furthermore, our results suggest MMP28 as a novel complementary marker in Chilblain LE diagnosis.