Stem cell factor and c-kit are expressed by and may affect vascular SMCs through an autocrine pathway.

Published

Journal Article

INTRODUCTION: Stem cell factor (SCF) is a membrane-bound and soluble growth factor that activates the c-kit tyrosine kinase receptor. Given the similarities between c-kit and platelet-derived growth factor (PDGF) receptors, we hypothesized that similar to PDGF, SCF/c-kit signaling may play a role in smooth muscle cell (SMC) function and thus the development of intimal hyperplasia. MATERIALS AND METHODS: Human saphenous vein SMCs were harvested from veins procured at the time of bypass grafting. Carotid arteries from rats that were balloon injured (n = 12) at variable time points were compared to sham-operated controls (n = 3). Expression of SCF and c-kit was measured by immunohistochemistry (IHC) and Western blotting. RESULTS: Western blotting revealed that human SMCs express membrane-bound SCF. In separate experiments, we found that this growth factor undergoes proteolytic cleavage to its soluble form following exposure to matrix metalloproteinase-9 (MMP-9), a ubiquitous MMP released at the time of arterial injury. We next evaluated in human SMCs, expression of the SCF receptor, c-kit. Western blotting of human SMC lysates revealed minor but consistent expression of c-kit. IHC demonstrated c-kit expression to be localized to the media. To determine if c-kit is up-regulated during the development of intimal hyperplasia, we evaluated expression of this receptor in a rat carotid balloon injury model. Quantification of IHC staining on injured vessels revealed that c-kit expression within the media was significantly increased at 3, 7, 14, and 28 days following injury (28.1, 30.8, 16, and 10.4% increase over sham controls, respectively, P < 0.05). Furthermore, c-kit expression was prominent within the neointima and maximal at 7 days (53.4 +/- 7.8% of area c-kit positive). CONCLUSION: Human vascular SMCs express the growth factor SCF and its receptor, c-kit. SCF is released from its membrane-bound form via MMP-9. This finding and the dramatic increase in c-kit expression observed in the rat carotid artery after balloon injury suggests SCF/c-kit signaling may affect SMC function via an autocrine pathway.

Full Text

Duke Authors

Cited Authors

  • Hollenbeck, ST; Sakakibara, K; Faries, PL; Workhu, B; Liu, B; Kent, KC

Published Date

  • August 2004

Published In

Volume / Issue

  • 120 / 2

Start / End Page

  • 288 - 294

PubMed ID

  • 15234225

Pubmed Central ID

  • 15234225

International Standard Serial Number (ISSN)

  • 0022-4804

Digital Object Identifier (DOI)

  • 10.1016/j.jss.2004.01.005

Language

  • eng

Conference Location

  • United States