title: Specific disruption of Lnk in murine endothelial progenitor cells promotes dermal wound healing via enhanced vasculogenesis, activation of myofibroblasts, and suppression of inflammatory cell recruitment.
abstract: Although endothelial progenitor cells (EPCs) contribute to wound repair by promoting neovascularization, the mechanism of EPC-mediated wound healing remains poorly understood due to the lack of pivotal molecular targets of dermal wound repair.
  
  
  
  We found that genetic targeting of the Lnk gene in EPCs dramatically enhances the vasculogenic potential including cell proliferation, migration, and tubule-like formation as well as accelerates in vivo wound healing, with a reduction in fibrotic tissue and improved neovascularization via significant suppression of inflammatory cell recruitment. When injected into wound sites, Lnk-/-EPCs gave rise to a significant number of new vessels, with remarkably increased survival of transplanted cells and decreased recruitment of cytotoxic T cells, macrophages, and neutrophils, but caused activation of fibroblasts in the wound-remodeling phase. Notably, in a mouse model of type I diabetes, transplanted Lnk-/-EPCs induced significantly better wound healing than Lnk+/+EPCs did.
  
  
  
  The specific targeting of Lnk may be a promising EPC-based therapeutic strategy for dermal wound healing via improvement of neovascularization but inhibition of excessive inflammation as well as activation of myofibroblasts during dermal tissue remodeling.
authors: Department of Pharmacology and Toxicology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, 35294, USA.
authors: Jun Hee
authors: JH
authors: Lee
authors: Department of Physiology, Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan, 626-870, Republic of Korea.
authors: Seung Taek
authors: ST
authors: Ji
authors: Research Institute of Convergence Biomedical Science and Technology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors: Jaeho
authors: J
authors: Kim
authors: Department of Immune Regulation, Research Centre for Hepatitis and Immunology, Research Institute, National Centre for Global Health and Medicine, Chiba, Japan.
authors: Satoshi
authors: S
authors: Takaki
authors: Department of Regenerative Medicine Science, Tokai University School of Medicine, Kanagawa, Japan.
authors: Takayuki
authors: T
authors: Asahara
authors: Division of Cardiology of Chonnam National University Hospital, Cardiovascular Convergence Research Center Nominated by Korea Ministry of Health and Welfare, Gwangju, 501-757, Republic of Korea. hyj200@hanmail.net.
authors: Young-Joon
authors: YJ
authors: Hong
authors: Department of Physiology, Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan, 626-870, Republic of Korea. smkwon323@hotmail.com.
authors: Sang-Mo
authors: SM
authors: Kwon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D066026:Endothelial Progenitor Cells / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008264:Macrophages / Q000502:physiology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D058628:Myofibroblasts / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D014945:Wound Healing / Q000235:genetics* / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; C490777:Lnk protein, mouse; D008565:Membrane Proteins
keywords: Anti-inflammatory; Cell-based therapy; Endothelial progenitor cell; Neovascularization; Wound healing