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.

MAP17 and the double-edged sword of ROS

“…Taken together, the Th cell cytokine-induced upregulation of MAP17 expression may be linked to the downregulation of filaggrin, which may be associated with the abnormal epidermal differentiation observed in the dermatological diseases [55].…”

“…In a meta-analysis of public microarray databases for different skin diseases, Noh et al [55] discovered that MAP17 is commonly upregulated, suggesting that it may be associated with abnormal keratinocyte differentiation. MAP17 was significantly upregulated in response to interferon-gamma, interleukin 4 (IL-4), IL-6, IL-17A or IL-22 in normal human epidermal keratinocytes.…”

“…Interestingly, 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, these authors [55] found that the over-expression of MAP17 in…”

Chemical allergens stimulate human epidermal keratinocytes to produce lymphangiogenic vascular endothelial growth factor

“…The cytokine concentration to elicit the response of NHKs and the ELISA measurement of VEGF after 24 h of the cytokine treatment were determined from our previous studies (Jin et al, 2014;Noh et al, 2010). Treatment with IL-1α and TNFα cytokines, which are known to be important in innate immunity, resulted in increased VEGF production by NHKs (Figs.…”

SKINOMICS: Transcriptional Profiling in Dermatology and Skin Biology

“…For example, the OncoMINE database uses a large collection of microarray data to identify genes differentially expressed in cancer or among different cancer types (https://www.oncomine.org/resource/login.html) [9]. Dr Noh and his group were among the first to use metaanalysis of microarray data in dermatology [10].…”