Deimination and Peptidylarginine Deiminases in Skin Physiology and Diseases

Abstract

Deimination, also known as citrullination, corresponds to the conversion of the amino acid arginine, within a peptide sequence, into the non-standard amino acid citrulline. This post-translational modification is catalyzed by a family of calcium-dependent enzymes called peptidylarginine deiminases (PADs). Deimination is implicated in a growing number of physiological processes (innate and adaptive immunity, gene regulation, embryonic development, etc.) and concerns several human diseases (rheumatoid arthritis, neurodegenerative diseases, female infertility, cancer, etc.). Here, we update the involvement of PADs in both the homeostasis of skin and skin diseases. We particularly focus on keratinocyte differentiation and the epidermal barrier function, and on hair follicles. Indeed, alteration of PAD activity in the hair shaft is responsible for two hair disorders, the uncombable hair syndrome and a particular form of inflammatory scarring alopecia, mainly affecting women of African ancestry.

Exploring the wound healing, anti-inflammatory, anti-pathogenic and proteomic effects of lactic acid bacteria on keratinocytes

“…Furthermore, SGL 07 and SGL 19 lysates induced the keratinocyte expression of protein-arginine deiminase type-1 (PADI1), 7.22-fold and 4.58-fold respectively. PADI1, immunodetected in all the neo-epidermis, catalyzes the conversion of protein-bound arginines into citrullines, a deimination process which involves clot proteins and that is fundamental for the wound closure 46,47 . The results of migration assays indicated that the L. plantarum SGL 07 and L. salivarius SGL 19 lysates accelerate the wound closure likely by enhancing the movement of keratinocytes.…”

Post-Translational Protein Deimination Signatures in Serum and Serum-Extracellular Vesicles of Bos taurus Reveal Immune, Anti-Pathogenic, Anti-Viral, Metabolic and Cancer-Related Pathways for Deimination

“…Calcium is a key modulator in a range of immunological, metabolic and developmental functions [199][200][201][202]. Calcium signalling is linked to a wide range of physiological and pathological processes [203][204][205], is a key driver for post-translational deimination [206][207][208] and plays an important role in the regulation of EVs [11,48]. In cattle, calcium is linked to many immunological pathways including inflammatory diseases [209], virus replication [210], parasitic infection [211], wound healing [212], reproduction [213,214] and adrenal function [215].…”

Deimination Protein Profiles in Alligator mississippiensis Reveal Plasma and Extracellular Vesicle-Specific Signatures Relating to Immunity, Metabolic Function, and Gene Regulation

“…PADs and associated protein deimination are crucial players in cancer and autoimmune and neurodegenerative diseases (17,19,20,22,25). PADs have received particular attention due to roles in cancer (20,22,26,27), rheumatoid arthritis (28)(29)(30)(31)(32)(33), multiple sclerosis (34)(35)(36)(37)(38), as well as due to their contribution to skin physiology and diseases (39). PADs have furthermore been shown to play crucial roles in hypoxia and CNS regeneration (40)(41)(42)(43)(44), and roles for PAD2 in promotion of oligodendrocyte differentiation and myelination have been shown (45).…”