Integrin-linked kinase (ILK) modulates wound healing through regulation of hepatocyte growth factor (HGF)

Journal Article · Thu Nov 15 00:00:00 EST 2012 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2012.08.001· OSTI ID:22212617

Serrano, Isabel; Diez-Marques, Maria L.; Rodriguez-Puyol, Manuel ^[1]; Investigacion Renal Cooperativa, Red de ^[2]; Herrero-Fresneda, Inmaculada ^[3]; Investigacion Renal Cooperativa, Red de ^[2]; Garcia del Moral, Raimundo ^[4]; Investigacion Renal Cooperativa, Red de ^[2]; Dedhar, Shoukat ^[5]; Investigacion Renal Cooperativa, Red de ^[2]; Rodriguez-Puyol, Diego ^[6]; Investigacion Renal Cooperativa, Red de ^[2]

---

1. Department of Physiology, University of Alcala, Alcala de Henares, Madrid (Spain)
2. RedinRen; Spain
3. Nephrology Unit, IDIBELL, Hospital de Bellvitge, Barcelona (Spain)
4. Department of Pathology, University of Granada (Spain)
5. Department of Integrative Oncology, BC Cancer Research Center, Vancouver, BC (Canada)
6. Nephrology Unit, Hospital Universitario Principe de Asturias, Alcala de Henares, Madrid (Spain)

Integrin-linked kinase (ILK) is an intracellular effector of cell-matrix interactions and regulates many cellular processes, including growth, proliferation, survival, differentiation, migration, invasion and angiogenesis. The present work analyzes the role of ILK in wound healing in adult animals using a conditional knock-out of the ILK gene generated with the tamoxifen-inducible Cre-lox system (CRE-LOX mice). Results show that ILK deficiency leads to retarded wound closure in skin. Intracellular mechanisms involved in this process were analyzed in cultured mouse embryonic fibroblast (MEF) isolated from CRE-LOX mice and revealed that wounding promotes rapid activation of phosphatidylinositol 3-kinase (PI3K) and ILK. Knockdown of ILK resulted in a retarded wound closure due to a decrease in cellular proliferation and loss of HGF protein expression during the healing process, in vitro and in vivo. Alterations in cell proliferation and wound closure in ILK-deficient MEF or mice could be rescued by exogenous administration of human HGF. These data demonstrate, for the first time, that the activation of PI3K and ILK after skin wounding are critical for HGF-dependent tissue repair and wound healing. -- Highlights: Black-Right-Pointing-Pointer ILK deletion results in decreased HGF expression and delayed scratch wound repair. Black-Right-Pointing-Pointer PI3K/ILK/AKT pathway signals through HGF to regulate wound healing. Black-Right-Pointing-Pointer An ILK-dependent increase in HGF expression is responsible for wound healing in vivo. Black-Right-Pointing-Pointer ILK-KO mice are used to confirm the requirement for ILK function in wound healing. Black-Right-Pointing-Pointer Human HGF treatment restores delayed wound closure in vitro and in vivo.

• OSTI ID: 22212617
• Journal Information: Experimental Cell Research, Vol. 318, Issue 19; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANGIOGENESIS
ANIMAL TISSUES
CELL PROLIFERATION
ERRORS
FIBROBLASTS
GROWTH FACTORS
HEALING
IN VITRO
IN VIVO
MICE
RNA
SKIN
TAMOXIFEN
WOUNDS