Authors: MarieClaire Méchin Fanny Coudane Véronique Adoue Jacques Arnaud Hélène Duplan Marie Charveron AnneMarie Schmitt Hidenari Takahara Guy Serre Michel Simon
Publish Date: 2010/01/29
Volume: 67, Issue: 9, Pages: 1491-1503
Abstract
Peptidylarginine deiminases PADs catalyze deimination converting arginyl to citrullyl residues Only three PAD isotypes are detected in the epidermis where they play a crucial role targeting filaggrin a key actor for the tissue hydration and barrier functions Their expression and activation depends on the keratinocyte differentiation state To investigate this regulation we used primary keratinocytes induced to differentiate either by increasing celldensity or by treatment with vitamin D High celldensity increased PAD1 and 3 but not PAD2 at the mRNA and protein levels and upregulated protein deimination By contrast vitamin D increased PAD1–3 mRNA amounts with distinct kinetics but neither the proteins nor the deimination rate Furthermore autodeimination was shown to decrease PAD activity increasing the distances between the four major amino acids of the active site In summary deimination can be regulated at multiple levels transcription of the PADI genes translation of the corresponding mRNAs and autodeimination of PADsWe thank C Pons for her excellent technical assistance the staff of the “Laboratoire de Biologie Cellulaire Cutanée du CERPER” especially I Cerutti M J Haure and S Julié for their technical advice the sequencing and genotyping facility of the IFR150 at ToulousePurpan particularly C Offer and H Brun for their precious high efficiency and the histological facility at ToulousePurpan especially F Capilla for her technical advice We are indebted to Dr A Ishigami Chiba Japan for the antiPAD2 antibody and to Drs H Palmer and G Carmeliet Cancer Research UK Cambridge Research Institute Cambridge UK for providing us with skin sections of VDRnull mice and control littermates We would also particularly like to thank N Mattiuzzo for his technical bioinformatics suggestions for performing VDRE sequences analysis and Drs M Sebbag and CY Hsu for their advice and helpful discussions This work was supported by grants from the “Centre National de la Recherche Scientifique” CNRS the “Société Française de Dermatologie” and the “Centre Européen de Recherche sur la Peau et les Epithéliums de Revêtement” CERPER Toulouse France and by the “Institut National de la Santé et de la Recherche Médicale” INSERM
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