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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:2115.)
© 2008 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

FRNK Expression Promotes Smooth Muscle Cell Maturation During Vascular Development and After Vascular Injury

Rebecca L. Sayers; Liisa J. Sundberg-Smith; Mauricio Rojas; Haruko Hayasaka; J. Thomas Parsons; Christopher P. Mack; Joan M. Taylor

From the Departments of Physiology (R.L.S.) and Pathology (L.J.S.-S., C.P.M., J.M.T.), and the Carolina Cardiovascular Biology Center (M.R., C.P.M., J.M.T.), University of North Carolina, Chapel Hill; and the Department of Microbiology (H.H., J.T.P.), University of Virginia Health System, Charlottesville.

Correspondence to Joan M. Taylor, Department of Pathology and Lab Medicine, 501 Brinkhous-Bullitt Bld. CB 7525, University of North Carolina, Chapel Hill, NC 27599-7525. E-mail jmt3x{at}med.unc.edu

Objective— Smooth muscle cell (SMC) differentiation is a dynamic process that must be tightly regulated for proper vascular development and to control the onset of vascular disease. Our laboratory previously reported that a specific focal adhesion kinase (FAK) inhibitor termed FRNK (FAK Related Non-Kinase) is selectively expressed in large arterioles when SMCs are transitioning from a synthetic to contractile phenotype and that FRNK inhibits FAK-dependent SMC proliferation and migration. Herein, we sought to determine whether FRNK expression modulates SMC phenotypes in vivo.

Methods and Results— We present evidence that FRNK^–/– mice exhibit attenuated SM marker gene expression during postnatal vessel growth and after vascular injury. We also show that FRNK expression is regulated by transforming growth factor (TGF)-β and that forced expression of FRNK in cultured cells induces serum- and TGF-β–stimulated SM marker gene expression, whereas FRNK deletion or expression of a constitutively activated FAK variant attenuated SM gene transcription.

Conclusions— These data highlight the possibility that extrinsic signals regulate the SMC gene profile, at least in part, by modulating the expression of FRNK and that tight regulation of FAK activity by FRNK is important for proper SMC differentiation during development and after vascular injury.

A specific focal adhesion kinase inhibitor termed FRNK is selectively expressed in medial smooth muscle cells in postnatal large arterioles. We found that ectopic expression of FRNK promotes smooth muscle maturation, whereas vessels from FRNK^–/– mice exhibit attenuated smooth muscle marker gene expression during postnatal growth and after vascular injury.

Key Words: integrins • smooth muscle • differentiation • vascular remodeling

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