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CCN2 promotes keratinocyte adhesion and migration via integrin α5β1
Elizabeth Kiwanuka1, Lauren Andersson, Edward J Caterson
1Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 2115, USA; Department of Surgical Sciences, Plastic Surgery Unit, Uppsala University, Uppsala, Sweden.
Experimental Cell Research
|August 31, 2013
Summary
Connective tissue growth factor (CCN2) enhances skin cell (keratinocyte) adhesion and migration by activating integrin α5β1 and the FAK-MAPK pathway. This finding clarifies CCN2's role in skin healing and cell movement.
Area of Science:
- Cell Biology
- Dermatology
- Biochemistry
Background:
- Connective tissue growth factor (CCN2) is known to regulate cell migration, with established roles in fibrosis.
- However, its specific effects on keratinocyte function, particularly adhesion and migration, remain less understood.
- This study aimed to elucidate the mechanisms underlying CCN2-driven keratinocyte responses.
Purpose of the Study:
- To investigate how CCN2 influences keratinocyte adhesion and migration.
- To identify the specific molecular pathways and receptors involved in CCN2-mediated keratinocyte function.
- To understand the role of integrins and intracellular signaling cascades in these processes.
Main Methods:
- Keratinocyte adhesion assays were conducted using fibronectin-coated surfaces with varying concentrations of CCN2 and inhibitors.
- Cell migration was assessed using modified Boyden chamber assays.
- Quantitative PCR and Western blotting were employed to analyze integrin expression and signaling pathway activation (FAK-MAPK).
Main Results:
- CCN2 significantly enhanced keratinocyte adhesion to fibronectin, primarily mediated by integrin α5β1.
- Blocking integrin α5β1 or inhibiting the FAK-MAPK pathway (using PD98059) attenuated CCN2-induced keratinocyte migration.
- CCN2 modulated the mRNA and protein expression of integrin subunits α5 and β1.
Conclusions:
- CCN2 promotes keratinocyte adhesion and migration through the integrin α5β1 receptor.
- The FAK-MAPK signaling cascade is crucial for CCN2's effects on keratinocyte migration.
- These findings provide mechanistic insights into CCN2's role in skin biology and wound healing.
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