TY - JOUR
T1 - Pannexin-3 Deficiency Delays Skin Wound Healing in Mice due to Defects in Channel Functionality
AU - Zhang, Peipei
AU - Ishikawa, Masaki
AU - Rhodes, Craig
AU - Doyle, Andrew
AU - Ikeuchi, Tomoko
AU - Nakamura, Kuniyuki
AU - Chiba, Yuta
AU - He, Bing
AU - Yamada, Yoshihiko
N1 - Funding Information:
This work was supported in part by the Intramural Research Program of National Institute of Dental and Craniofacial Research, National Institutes of Health (YY) and by the National Institute of Dental and Craniofacial Research Gene Transfer Core Facility ( ZIC DE000744-04 ) (YY). This work was also supported by the Japan Society for the Promotion of Science KAKENHI , Grant-in-Aid (TI and YC) and by the National Natural Science Foundation of China ( NSFC81500811 to BH).
Publisher Copyright:
© 2018 The Authors
PY - 2019/4
Y1 - 2019/4
N2 - Pannexin-3 (Panx3) is a gap junction protein that is required for regulating cell cycle exit and the differentiation of osteoblasts and chondrocytes during skeletal development. However, the role of Panx3 in skin tissue regeneration remains unclear. After dorsal skin punch biopsies, Panx3-knockout mice exhibited a significant delay in wound healing with insufficient re-epithelialization, decreased inflammatory reaction, and reduced collagen remodeling. Panx3 expression coincided with inflammatory reactions both in vivo and in vitro. By applying exogenous tumor necrosis factor-α to mimic inflammation in vitro, Panx3 expression was induced in HaCaT cells. In addition, Panx3 depletion reduced epithelial-mesenchymal transition during skin wound healing. A protein essential for signaling in epithelial-mesenchymal transition, transforming growth factor-β interacted with Panx3 by modulating intracellular adenosine triphosphate levels and thereby enhanced HaCaT cell migration ability with Panx3 overexpression. In conclusion, Panx3 plays a key role in the skin wound healing process by controlling keratinocytes and keratinocyte-mesenchyme cross-talk via hemichannel and endoplasmic reticulum Ca 2+ channel functions, which differs from another gap junction, connexin 43 (Cx43), during skin wound healing.
AB - Pannexin-3 (Panx3) is a gap junction protein that is required for regulating cell cycle exit and the differentiation of osteoblasts and chondrocytes during skeletal development. However, the role of Panx3 in skin tissue regeneration remains unclear. After dorsal skin punch biopsies, Panx3-knockout mice exhibited a significant delay in wound healing with insufficient re-epithelialization, decreased inflammatory reaction, and reduced collagen remodeling. Panx3 expression coincided with inflammatory reactions both in vivo and in vitro. By applying exogenous tumor necrosis factor-α to mimic inflammation in vitro, Panx3 expression was induced in HaCaT cells. In addition, Panx3 depletion reduced epithelial-mesenchymal transition during skin wound healing. A protein essential for signaling in epithelial-mesenchymal transition, transforming growth factor-β interacted with Panx3 by modulating intracellular adenosine triphosphate levels and thereby enhanced HaCaT cell migration ability with Panx3 overexpression. In conclusion, Panx3 plays a key role in the skin wound healing process by controlling keratinocytes and keratinocyte-mesenchyme cross-talk via hemichannel and endoplasmic reticulum Ca 2+ channel functions, which differs from another gap junction, connexin 43 (Cx43), during skin wound healing.
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U2 - 10.1016/j.jid.2018.08.033
DO - 10.1016/j.jid.2018.08.033
M3 - Article
C2 - 30389492
AN - SCOPUS:85061328306
SN - 0022-202X
VL - 139
SP - 909
EP - 918
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 4
ER -