title: Inositol kinase and its product accelerate wound healing by modulating calcium levels, Rho GTPases, and F-actin assembly.
abstract: Wound healing is essential for survival. We took advantage of the Xenopus embryo, which exhibits remarkable capacities to repair wounds quickly and efficiently, to investigate the mechanisms responsible for wound healing. Previous work has shown that injury triggers a rapid calcium response, followed by the activation of Ras homolog (Rho) family guanosine triphosphatases (GTPases), which regulate the formation and contraction of an F-actin purse string around the wound margin. How these processes are coordinated following wounding remained unclear. Here we show that inositol-trisphosphate 3-kinase B (Itpkb) via its enzymatic product inositol 1,3,4,5-tetrakisphosphate (InsP4) plays an essential role during wound healing by modulating the activity of Rho family GTPases and F-actin ring assembly. Furthermore, we show that Itpkb and InsP4 modulate the speed of the calcium wave, which propagates from the site of injury into neighboring uninjured cells. Strikingly, both overexpression of itpkb and exogenous application of InsP4 accelerate the speed of wound closure, a finding that has potential implications in our quest to find treatments that improve wound healing in patients with acute or chronic wounds.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, United Kingdom.
authors.forename: Ximena
authors.initials: X
authors.lastname: Soto
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.forename: Robert
authors.initials: R
authors.lastname: Lea
authors.forename: Eamon
authors.initials: E
authors.lastname: Dubaissi
authors.forename: Nancy
authors.initials: N
authors.lastname: Papalopulu
authors.forename: Enrique
authors.initials: E
authors.lastname: Amaya
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D004475:Ectoderm / Q000196:embryology / Q000502:physiology; D004817:Epidermis / Q000196:embryology / Q000502:physiology; D005260:Female; D055785:Gene Knockdown Techniques; D007295:Inositol Phosphates / Q000502:physiology; D009865:Oocytes / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*; D029867:Xenopus Proteins / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; D007295:Inositol Phosphates; D029867:Xenopus Proteins; C519007:inositol 1,2,3,4-tetraphosphate 5,6-dipyrophosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase; D020741:rho GTP-Binding Proteins; D002118:Calcium