Renz et al. (2019) noted that the genodermatosis IWC is caused by dominant-negative variants that result in aberrant KRT10 proteins that localize to the nucleus rather than the cytoplasm. The mislocalization is associated with a C terminus that is altered from a polyglycine tail to either a polyarginine or polyalanine tail. Renz et al. (2019) demonstrated that only K10 with an arginine-rich C terminus (K10arg) translocates to the nucleus, whereas wildtype K10, K10ala, and truncated K10 remain in the cytoplasm. The authors also showed that the presence of K10arg enables cotranslocation of non-K10arg proteins into the nucleus. They concluded that arginine-rich K10 tails are responsible for the pathogenic nuclear localization of K10 in patients with IWC. Conlin PA, Rapini RP. Epidermolytic hyperkeratosis associated with melanocytic nevi: a report of 53 cases. Am J Dermatopathol 2002; 24: 23–5. DOI: 10.1097/00000372-200202000-00004. PubMed

In this study, we also excluded the possibility that DcR3-mediated regulation of differentiation marker expression results from an indirect action on cell growth. We found that DcR3 silencing does not alter cell growth, possibly because the initiation of keratinocyte differentiation is not inseparably associated with cell cycle arrest 42. On the other hand, the positive EGFR-DcR3 loop mentioned above was verified by additional findings. First, during keratinocyte differentiation induced by PMA treatment, calcium treatment or cell confluence, EGFR activity was time-dependently decreased gradually. This change in EGFR activity kinetics occurred in parallel to the downregulation of DcR3 mRNA expression. Second, the observation that suppression of DcR3 gene expression was enhanced by the EGFR inhibitor gefitinib during differentiation in the models suggests the role of EGFR in DcR3 gene expression. However, before the time-dependent decrease in DcR3 during keratinocyte differentiation, we observed transient induction of DcR3 expression by PMA (within 6 h) and calcium (within 12 h) treatment, and this effect was independent of EGFR activity. Currently, we do not have other data to clarify the mechanisms and cellular functions of this transient increase in DcR3 gene expression. To determine the relative cell number, NHEKs transfected with the indicated siRNA were cultured in medium with or without growth factors for 5 days. After rinsing with phosphate-buffered saline (PBS), cells were fixed with methanol for 10 min at room temperature and were then stained with 0.1% crystal violet. The relative cell number was determined by measuring the absorbance of the dissolved dye at 540 nm after elution with 33% acetic acid. Cell counting and cell cycle analysis Tsujikawa K et al. Developmentally interdependent stretcher-compressor relationship between the embryonic brain and the surrounding scalp in the preosteogenic head. Dev Dyn 251:1107-1122 (2022). Autosomal recessive;Autosomal recessive form;Autosomal recessive predisposition;biallelic_autosomal Spoerri, I., Brena, M., De Mesmaeker, J., Schlipf, N., Fischer, J., Tadini, G., Itin, P. H., Burger, B.Characterization of a novel human type II epithelial keratin K1b, specifically expressed in eccrine sweat glands. In a 7-month-old boy with IWC, Saito et al. (2017) identified heterozygosity for the recurrent KRT10 c.1374-1G-C splicing mutation ( 148080.0023), which had previously been reported in 3 patients with IWC.

Publishing research using ab9025? Please let us know so that we can cite the reference in this datasheet. Ruiz-Torres S et al. Inherited DNA Repair Defects Disrupt the Structure and Function of Human Skin. Cell Stem Cell 28:424-435.e6 (2021). Rothnagel, J. A., Dominey, A. M., Dempsey, L. D., Longley, M. A., Greenhalgh, D. A., Gagne, T. A., Huber, M., Frenk, E., Hohl, D., Roop, D. R. Chang, Y. C. et al. Modulation of macrophage differentiation and activation by decoy receptor 3. J. Leukoc. Biol. 75, 486–494 (2004). Kim, S., Fotiadu, A. & Kotoula, V. Increased expression of soluble decoy receptor 3 in acutely inflamed intestinal epithelia. Clin. Immunol. 115, 286–294 (2005).Rothnagel JA, Longley MA, Holder RA, etal. (1994). "Prenatal diagnosis of epidermolytic hyperkeratosis by direct gene sequencing". J. Invest. Dermatol. 102 (1): 13–6. doi: 10.1111/1523-1747.ep12371723. PMID 7507150. Covaciu, C., Castori, M., De Luca, N., Ghirri, P., Nannipieri, A., Ragone, G., Zambruno, G., Castiglia, D. The prognosis of epidermolytic ichthyosis is variable and depends on the severity of the symptoms. There is an immediate risk of dehydration, infection, sepsis, and premature death. Patients who survive experience infection, skin fragility, and blistering episodes throughout their lives, in addition to stress and social isolation accompanying these symptoms [1,2].

Our study also showed the role of the extracellular action of DcR3 in keratinocyte differentiation. Via the conditioned medium approach, we found that exogenous DcR3 reversed the effects of DcR3 silencing on upregulating keratin 10 and loricrin gene expression but failed to change DcR3 silencing-induced downregulation of TGase 1 and involucrin. These findings not only reveal the gene-specific regulation by DcR3 and EGF but also indicate that DcR3 serves as an effector via its extracellular action. Several lines of evidence indicate that TL1A may be involved in the pathogenesis of psoriasis 20, 46. Other ligands neutralized by DcR3, such as FasL and LIGHT, have been shown to regulate keratinocyte death 46, keratinocyte-mediated skin inflammation and fibrosis 47, 48, but their effects on keratinocyte differentiation are unknown. Although we cannot exclude the possibility of interactions between DcR3 and these ligands in regulating keratinocyte differentiation, more studies are required to explore other possible soluble factors regulated by DcR3 in keratinocytes. Genetic mutations in the K1 and K10 genes of patients with epidermolytic hyperkeratosis. Correlation between location and disease severity.Polkoff KM et al. LGR5 is a conserved marker of hair follicle stem cells in multiple species and is present early and throughout follicle morphogenesis. Sci Rep 12:9104 (2022). A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Burger, B., Ghosh, A., Ng, C. K. Y., Piscuoglio, S., Spoerri, I., Itin, P. H., Greer, K., Elbaum, D. Herro, R. et al. LIGHT–HVEM signaling in keratinocytes controls development of dermatitis. J. Exp. Med. 215, 415–422 (2018). Cohen, G. et al. Epidermal growth factor receptor signaling is up-regulated in human colonic aberrant crypt foci. Cancer Res. 66, 5656–5664 (2006).