title: Deimination and expression of peptidylarginine deiminases during cutaneous wound healing in mice.
abstract: Deimination, the conversion of protein-bound arginines into citrullines, is a post-translational modification catalyzed by a peptidylarginine deiminase (Pad). In the epidermis, three Pads are expressed, namely Pad1, 2 and 3, and the major deiminated protein is filaggrin. Deimination of fibrin has been observed in various pathological inflammatory conditions. Here, we analyzed the expression of Pads and citrullination of proteins during cutaneous wound healing, i.e. in a physiological inflammatory condition. Full-thickness punches were performed on adult mouse back skin, and wound recovery was analyzed over 10 days by immunohistology and western blotting. Pad1 was immunodetected in all the neo-epidermis. Pad3, normally expressed in the stratum granulosum, was not detected in the hyperproliferative tongue of the neo-epidermis, but was shown to be co-localized with (pro)filaggrin in a large number of keratinocyte layers in its differentiating part. Deiminated proteins were detected in the stratum corneum of the neo-epidermis in the late phase of re-epithelialization, and in the clot and the clot-derived scab. In the clot where we only detected Pad4, one of the deiminated proteins was shown to be fibrin. Deimination of the clot proteins, and more generally wound healing and keratinocyte differentiation, seemed to be Pad2-independent, as shown using Padi2(-/-) mice.
authors.affiliation: CNRS-Université Toulouse III, CHU Purpan, 31059 Toulouse, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Coudane
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Mechin
authors.forename: Anne
authors.initials: A
authors.lastname: Huchenq
authors.forename: Julie
authors.initials: J
authors.lastname: Henry
authors.forename: Rachida
authors.initials: R
authors.lastname: Nachat
authors.forename: Akihito
authors.initials: A
authors.lastname: Ishigami
authors.forename: Véronique
authors.initials: V
authors.lastname: Adoue
authors.forename: Mireille
authors.initials: M
authors.lastname: Sebbag
authors.forename: Guy
authors.initials: G
authors.lastname: Serre
authors.forename: Michel
authors.initials: M
authors.lastname: Simon
mesh_terms: D000818:Animals; D001706:Biopsy; D015153:Blotting, Western; D002454:Cell Differentiation; D004195:Disease Models, Animal; D006867:Hydrolases / Q000096:biosynthesis*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000080064:Protein-Arginine Deiminase Type 2; D000076342:Protein-Arginine Deiminases; D012867:Skin / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000378:metabolism* / Q000473:pathology
chemical_list: D006867:Hydrolases; C000620353:Padi2 protein, mouse; D000080064:Protein-Arginine Deiminase Type 2; D000076342:Protein-Arginine Deiminases