APN/CD13 is over‐expressed by Psoriatic fibroblasts and is modulated by CGRP and IL‐4 but not by retinoic acid treatment

• Published in: Journal of cellular physiology Vol. 233; no. 2; pp. 958 - 967
• Main Authors: Gerbaud, Pascale, Guibourdenche, Jean, Jarray, Rafika, Conti, Marc, Palmic, Patricia, Leclerc‐Mercier, Stéphanie, Bruneau, Julie, Hermine, Olivier, Lepelletier, Yves, Raynaud, Françoise
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.02.2018; Wiley
• Subjects: Adult; Aged; aminopeptidase‐N; Blocking antibodies; Calcitonin; Calcitonin gene-related peptide; Calcitonin Gene-Related Peptide - pharmacology; Case-Control Studies; CD13 antigen; CD13 Antigens - genetics; CD13 Antigens - metabolism; Cells, Cultured; CGRP; Enzymatic activity; Female; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - enzymology; Fibroblasts - pathology; Gene expression; Humans; Interleukin 4; Interleukin-4 - pharmacology; Life Sciences; Male; Middle Aged; Overexpression; Plaques; Psoriasis; Psoriasis - enzymology; Psoriasis - genetics; Psoriasis - pathology; Psoriasis vulgaris; Retinoic acid; Skin; Skin - drug effects; Skin - enzymology; Skin - pathology; Skin diseases; Time Factors; Tretinoin - pharmacology; Up-Regulation; interleukin-4; fibroblasts; CGRP; psoriasis; aminopeptidase-N
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.25941

Psoriasis vulgaris is a common skin inflammatory disease characterized by recurrent flare episodes associated with scaly well‐demarcated skin plaques. Skin biopsies from psoriatic patients with high PASI score (22.67 ± 8.67) and from HD were used to study APN/CD13. APN/CD13 is over‐expressed in LP and nLP compare to HD skins and fibroblasts. This over‐expression is positively correlated with specific enzymatic activity enhancement. However, discrepancies between APN/CD13 expression in LP and nLP prompt us to focus our study on APN/CD13 modulation. Calcitonin Gene Related Peptide (CGRP), a neuropeptide, positively modulated expression and activity of APN/CD13. CGRP consistently induced IL4 secretion, which is also involved in the increase of APN/CD13 expression and activity, which is significantly reversed using IL‐4 blocking antibody. Surprisingly, retinoic acid altered the APN/CD13 enzymatic activity only in nLP fibroblasts without modification of APN/CD13 expression. APN/CD13 is over‐expressed on psoriatic fibroblasts and exerted high level of activity compare to HD fibroblasts. Taken together, several factors such as CGRP and IL‐4 acted on positive regulation of APN/CD13 expression and activity. This study highlighted the interest of APN/CD13 as a new potential target, which should be investigated in psoriasis. APN/CD13 aminopeptidase‐N is upregalated in sporiatic skins compare to healthy donors. APN/CD13 is mostly increased in nLP (non lesional psoriatic) compare to LP (lesional psoriatic) skins. APN/CD13 is positively regulated by IL‐4 and CGRP.