Heparin-binding EGF-like growth factor (HB-EGF) promotes cell migration and adhesion via focal adhesion kinase

Abstract

Background Cell migration and adhesion are essential in intestinal epithelial wound healing and recovery from injury. Focal adhesion kinase (FAK) plays an important role in cell-extra cellular matrix (ECM) signal transduction. We have previously shown that heparin-binding epidermal growth factor-like growth factor (HB-EGF) promotes intestinal epithelial cell (IEC) migration and adhesion in vitro. The current study was designed to determine whether FAK is involved in HB-EGF-induced IEC migration and adhesion. Materials and Methods A scrape wound healing model of rat intestinal epithelial cells (RIE-1 cells) was used to examine the effect of HB-EGF on FAK-dependent cell migration in vitro. Immunofluorescence and Western blot analyses were performed to evaluate the effect of HB-EGF on the expression of phosphorylated FAK (p-FAK). Cell adhesion assays were performed to determine the role of FAK in HB-EGF-induced cell adhesion on fibronectin (FN). Results HB-EGF significantly increased healing after scrape wounding, an effect that was reversed in the presence of a FAK inhibitor (FAK I-14) (both with p<0.05). HB-EGF increased p-FAK expression, and induced p-FAK redistribution and actin reorganization in migrating RIE-1 cells. Cell adhesion and spreading on FN were significantly increased by HB-EGF (p<0.05). FAK I-14 significantly inhibited both intrinsic and HB-EGF-induced cell adhesion and spreading on FN (both with p<0.05). Conclusions FAK phosphorylation and FAK-mediated signal transduction play essential roles in HB-EGF-mediated IEC migration and adhesion.

Galectin-3 enhances extracellular matrix associations and wound healing in monkey corneal epithelium

“…In rodent models, exogenous galectin-3 accelerated re-epithelialization after alkali burn and mechanical abrasion (Cao et al, 2002; Yabuta et al, 2014). Similar examples include experiments showing that β-glucan, ROCK inhibitor, and heparin-binding EGF-like growth factor promote cell adhesion and wound healing in corneal epithelial cells, corneal endothelial cells, and intestinal epithelial cells, respectively (Choi and Joo, 2013; Pipparelli et al, 2013; Su and Besner, 2014). This indicates that ECMs are essential for cell migration in corneal wound healing.…”

A Novel Endogenous Damage Signal, CSF-2, Activates Multiple Beneficial Functions of Adipose Tissue-Derived Mesenchymal Stem Cells

“…Importantly, we also found that CSF-2 significantly enhances the therapeutic capability of stem cells by promoting multi-lineage differentiation (Figure 2A) and migratory capability ( Figures 2D and 2E) in vitro. In addition, CSF-2-treated stem cells actively secreted many known growth factors for promoting tissue regeneration, specifically, AR, 40 G-CSF, 41 GDNF, 42 GM-CSF, 9 HB-EGF, 43 and PDGF 44 ( Figure 6). These results suggest that the CSF-2-mediated beneficial effects of stem cells on tissue regeneration were due, at least in part, to the various secretory factors that regulate diverse biological functions, including cell growth, wound healing, and differentiation.…”

Exosomes secreted from bone marrow-derived mesenchymal stem cells protect the intestines from experimental necrotizing enterocolitis

“…Scrape wounding was performed as previously described [36], [37]. IEC-6 cells were seeded to each well of a 12 well plate at 80% confluence and incubated in DMEM/F12/Glutamax-I™ (Gibco Invitrogen, Carlsbad, CA) supplemented with 10% FBS at 37°C in 5% CO 2 .…”