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Pannexin 3 deficiency impairs skin development and delays wound healing in mice via its hemichannel and ER Ca2+ channel functions

Wednesday, September 13, 2017 — Poster Session I

12:00 p.m. – 1:30 p.m.
FAES Terrace
NIDCR
DEVBIO-8

Authors

  • P Zhang
  • M Ishikawa
  • C Rhodes
  • A Doyle
  • T Ikeuchi
  • K Nakamura
  • Y Chiba
  • Y Yamada

Abstract

Pannexin 3 (Panx3), a gap junction protein, is required for skeletal development. However, its role in skin tissue regeneration remains unclear. Here, we demonstrate that Panx3 regulates skin development and wound healing via its hemichannel and endoplasmic reticulum (ER) Ca2+ channel functions. Transfection of the human HACAT keratinocyte cell line with Panx3 cDNA for Panx3 over-expression or Panx3 shRNA for Panx3 knockdown revealed that low levels of Panx3 expression were critical for keratinocyte proliferation, whereas high levels of Panx3 expression induced differentiation. Panx3 also promoted keratinocyte migration during the epithelial–mesenchymal transition (EMT). Panx3 overexpression increased the release of cellular ATP into the extracellular space via the Panx3 hemichannel and induced Ca2+ release from the ER to the cytosol via the Panx3 ER Ca2+ channel. Panx3 knockout (KO) mice showed impaired skin development and delayed hair follicle regeneration when compared to their control Panx3-heterozygous knockout siblings. Panx3 KO mice also showed delayed wound closure and less re-epithelialization, less collagen remodeling, and decreases in inflammatory markers, EMT markers, and cell signaling pathways markers, including Wnt, BMP, and TGF-¿. Panx3 therefore plays a key role in skin development and wound healing via its hemichannel, gap junction, and ER Ca2+ channel functions.

Category: Developmental Biology