TY - JOUR
T1 - Pannexin 3 regulates skin development via Epiprofin
AU - Zhang, Peipei
AU - Ishikawa, Masaki
AU - Doyle, Andrew
AU - Nakamura, Takashi
AU - He, Bing
AU - Yamada, Yoshihiko
N1 - Funding Information:
We thank Kenneth Yamada for critical suggestions. This work was supported in part by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, USA [Grant Number DE000483-24, -25, and-26 to Y.Y.]; Grants-in-Aid from the Ministry of Education, Science, and Culture of Japan [Grant Number 16H05514 to M.I.]; Grants-in-Aid for Scientific Research-KAKENHI-Challenging Research (Exploratory) [Grant Number 19K22698 to M.I.and 18K19634 to T.N.]; Grants-in-Aid for Scientific Research-KAKENHI-Fostering Joint International Research [Grant Number 16KK0196 to M.I.]; the National Nature Science Foundation of China [NSFC81500811 to B.H.]. M.I. was supported in part by a Research Fellowship from the Japan Society for the Promotion of Science for Young Scientists.
PY - 2021/12
Y1 - 2021/12
N2 - Pannexin 3 (Panx3), a member of the gap junction pannexin family is required for the development of hard tissues including bone, cartilage and teeth. However, the role of Panx3 in skin development remains unclear. Here, we demonstrate that Panx3 regulates skin development by modulating the transcription factor, Epiprofin (Epfn). Panx3−/− mice have impaired skin development and delayed hair follicle regeneration. Loss of Panx3 in knockout mice and suppression by shRNA both elicited a reduction of Epfn expression in the epidermis. In cell culture, Panx3 overexpression promoted HaCaT cell differentiation, cell cycle exit and enhanced Epfn expression. Epfn−/− mice and inhibition of Epfn by siRNA showed no obvious differences of Panx3 expression. Furthermore, Panx3 promotes Akt/NFAT signaling pathway in keratinocyte differentiation by both Panx3 ATP releasing channel and ER Ca2+ channel functions. Our results reveal that Panx3 has a key role factor for the skin development by regulating Epfn.
AB - Pannexin 3 (Panx3), a member of the gap junction pannexin family is required for the development of hard tissues including bone, cartilage and teeth. However, the role of Panx3 in skin development remains unclear. Here, we demonstrate that Panx3 regulates skin development by modulating the transcription factor, Epiprofin (Epfn). Panx3−/− mice have impaired skin development and delayed hair follicle regeneration. Loss of Panx3 in knockout mice and suppression by shRNA both elicited a reduction of Epfn expression in the epidermis. In cell culture, Panx3 overexpression promoted HaCaT cell differentiation, cell cycle exit and enhanced Epfn expression. Epfn−/− mice and inhibition of Epfn by siRNA showed no obvious differences of Panx3 expression. Furthermore, Panx3 promotes Akt/NFAT signaling pathway in keratinocyte differentiation by both Panx3 ATP releasing channel and ER Ca2+ channel functions. Our results reveal that Panx3 has a key role factor for the skin development by regulating Epfn.
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U2 - 10.1038/s41598-021-81074-1
DO - 10.1038/s41598-021-81074-1
M3 - Article
C2 - 33469169
AN - SCOPUS:85099606946
VL - 11
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 1779
ER -