title: MAP17 is associated with the T-helper cell cytokine-induced down-regulation of filaggrin transcription in human keratinocytes.
abstract: In the meta-analysis of public microarray databases for different skin diseases, we revealed seven commonly up-regulated genes, DSG3, KRT6, MAP17, PLSCR1, RPM2, SOD2 and SPRR2B. We postulated that the genes selected from the meta-analysis may be potentially associated with the abnormal keratinocyte differentiation. To demonstrate this postulation, we alternatively evaluated whether the genes of interest in the meta-analysis can be regulated by T-helper (Th) cell cytokines in normal human epidermal keratinocytes (NHEK). We found that MAP17 was significantly up-regulated in response to interferon-gamma, interleukin 4 (IL-4), IL-6, IL-17A or IL-22 in NHEK. Interestingly, MAP17 was originally reported to interact with PDZK1; in turn, the PDZK1 gene is localized within the atopic dermatitis-linked region on human chromosome 1q21. In an attempt to evaluate whether MAP17 regulates the expression of cornified envelope-associated genes at the 1q21 locus, such as filaggrin, loricrin and involucrin, we found that the over-expression of MAP17 in HaCaT keratinocytes significantly decreased the expression of filaggrin. Taken together, the Th cell cytokine-induced up-regulation of MAP17 expression may be linked to the down-regulation of filaggrin in NHEK, which may be associated with the abnormal epidermal differentiation observed in the dermatological diseases.
authors: Skin Research Institute, AmorePacific Corporation R&D Center, Yongin, Gyeounggi-do, Republic of Korea. minsoonoh@amorepacific.com
authors: Minsoo
authors: M
authors: Noh
authors: Hyeonju
authors: H
authors: Yeo
authors: Jaeyoung
authors: J
authors: Ko
authors: Han Kon
authors: HK
authors: Kim
authors: Chang-Hoon
authors: CH
authors: Lee
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D019295:Computational Biology; D016207:Cytokines / Q000494:pharmacology*; D030541:Databases, Genetic; D051184:Desmoglein 3 / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics*; D000091344:Filaggrin Proteins; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D020381:Interleukin-17 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D007381:Intermediate Filament Proteins / Q000235:genetics*; D053550:Keratin-10 / Q000235:genetics; D053553:Keratin-6 / Q000235:genetics; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics*; D049294:Phospholipid Transfer Proteins / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D012871:Skin Diseases / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*; D014162:Transfection; D011503:Transglutaminases / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D000097043:Interleukin-22; D000099156:Superoxide Dismutase 2
chemical_list: D016207:Cytokines; D051184:Desmoglein 3; D000091344:Filaggrin Proteins; D007371:Interferon-gamma; D020381:Interleukin-17; D015847:Interleukin-4; D007378:Interleukins; D007381:Intermediate Filament Proteins; D053550:Keratin-10; D053553:Keratin-6; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D011498:Protein Precursors; D013482:Superoxide Dismutase; D011503:Transglutaminases; D000097043:Interleukin-22; D000099156:Superoxide Dismutase 2; C071894:DSG3 protein, human; C000717249:FLG protein, human; C507493:KRT10 protein, human; C507569:KRT6A protein, human; C509768:PDZK1IP1 protein, human; C493422:PLSCR1 protein, human; C064554:loricrin; C032253:involucrin