Homeostasis of the skin barrier is essential for maintaining normal skin function.Gasdermin A(GSDMA)is highly expressed in the skin and associated with many skin diseases,such as melanoma and psoriasis.In mice,GSDMA i...Homeostasis of the skin barrier is essential for maintaining normal skin function.Gasdermin A(GSDMA)is highly expressed in the skin and associated with many skin diseases,such as melanoma and psoriasis.In mice,GSDMA is encoded by three gene homologues,namely Gsdma1,Gsdma2,and Gsdma3.Although Gsdma3 gain-of-function mutations cause hair loss and skin inflammation,Gsdma3-deficient mice do not show any visible phenotypes in skin and hair structures.To explore the physiological function of GSDMA,we generated conventional Gsdma1/2/3 knockout(KO)mice.These mice showed significantly alleviated epidermal hyperplasia and inflammation induced by phorbol 12-myristate 13-acetate(PMA).Furthermore,the alleviation of epidermal hyperplasia depended on the expression of Gsdma1/2/3 specifically in keratinocytes.Mechanistically,Gsdma1/2/3 depletion downregulated epidermal growth factor receptor(EGFR)ligands,leading to the decreased EGFR–Stat3/Akt signalling.These results demonstrate that depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia partially by inhibiting the EGFR–Stat3/Akt pathway.展开更多
基金supported by grants from the Ministry of Science and Technology of China(2018YFA0801100 and 2021YFF0702100)the National Natural Science Foundation of China(31971056,31772550,and 32000513)+1 种基金the Natural Science Foundation of Jiangsu Province(BK20181260)the Fundamental Research Funds for the Central Universities(14380516 and 021414380533).
文摘Homeostasis of the skin barrier is essential for maintaining normal skin function.Gasdermin A(GSDMA)is highly expressed in the skin and associated with many skin diseases,such as melanoma and psoriasis.In mice,GSDMA is encoded by three gene homologues,namely Gsdma1,Gsdma2,and Gsdma3.Although Gsdma3 gain-of-function mutations cause hair loss and skin inflammation,Gsdma3-deficient mice do not show any visible phenotypes in skin and hair structures.To explore the physiological function of GSDMA,we generated conventional Gsdma1/2/3 knockout(KO)mice.These mice showed significantly alleviated epidermal hyperplasia and inflammation induced by phorbol 12-myristate 13-acetate(PMA).Furthermore,the alleviation of epidermal hyperplasia depended on the expression of Gsdma1/2/3 specifically in keratinocytes.Mechanistically,Gsdma1/2/3 depletion downregulated epidermal growth factor receptor(EGFR)ligands,leading to the decreased EGFR–Stat3/Akt signalling.These results demonstrate that depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia partially by inhibiting the EGFR–Stat3/Akt pathway.
