| First Author | Kanemaru K | Year | 2017 |
| Journal | Cell Death Differ | Volume | 24 |
| Issue | 6 | Pages | 1079-1090 |
| PubMed ID | 28430185 | Mgi Jnum | J:268446 |
| Mgi Id | MGI:6269506 | Doi | 10.1038/cdd.2017.56 |
| Citation | Kanemaru K, et al. (2017) Phospholipase Cdelta1 regulates p38 MAPK activity and skin barrier integrity. Cell Death Differ 24(6):1079-1090 |
| abstractText | Keratinocytes undergo a unique type of programmed cell death known as cornification, which leads to the formation of the stratum corneum (SC), the main physical barrier of the epidermis. A defective epidermal barrier is a hallmark of the two most common inflammatory skin disorders, psoriasis, and atopic dermatitis. However, the detailed molecular mechanisms of skin barrier formation are not yet fully understood. Here, we showed that downregulation of phospholipase C (PLC) delta1, a Ca(2+)-mobilizing and phosphoinositide-metabolizing enzyme abundantly expressed in the epidermis, impairs the barrier functions of the SC. PLCdelta1 downregulation also impairs localization of tight junction proteins. Loss of PLCdelta1 leads to a decrease in intracellular Ca(2+) concentrations and nuclear factor of activated T cells activity, along with hyperactivation of p38 mitogen-activated protein kinase (MAPK) and inactivation of RhoA. Treatment with a p38 MAPK inhibitor reverses the barrier defects caused by PLCdelta1 downregulation. Interestingly, this treatment also attenuates psoriasis-like skin inflammation in imiquimod-treated mice. These findings demonstrate that PLCdelta1 is essential for epidermal barrier integrity. This study also suggests a possible link between PLCdelta1 downregulation, p38 MAPK hyperactivation, and barrier defects in psoriasis-like skin inflammation. |
