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(Circulation Research. 2008;102:1455.)
© 2008 American Heart Association, Inc.

Editorials

Krüppel-Like Factor 4

Transcriptional Regulator of Proliferation, or Inflammation, or Differentiation, or All Three?

Michael V. Autieri

From the Department of Physiology, Independence Blue Cross Cardiovascular Research Center, Temple University School of Medicine, Philadelphia Pa.

Correspondence to Michael Autieri, PhD, Department of Physiology, Temple University School of Medicine, Room 810, MRB, 3420 N Broad St, Philadelphia PA 19140. E-mail mautieri@temple.edu

See related article, pages 1548–1557

Key Words: Krüppel-like factor 4 • phenotypic switch • proliferation • transcription factor

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
The transcriptional response to vascular injury. The vascular response to injury is a dynamic and multifactorial process involving several cell types. As part of the vascular response to injury, normally quiescent, contractile vascular smooth muscle cells (VSMCs) respond to inflammatory and growth factors by transforming from a differentiated contractile state to a dedifferentiated synthetic phenotype capable of migration, proliferation, and synthesis of cytokines and extracellular matrix.¹ As the major effector cell in this occlusive process, the VSMC must coordinate and synchronize immensely complex inflammatory, proliferative, and differentiation programs. Indeed, the activated "myofibroblastic" VSMCs can even express proteins and cytokines ascribed to be restricted to inflammatory cells.^2,3 Several transcription factors have earned the moniker of "master switch" of inflammation (eg, NF-B), or proliferation (eg, Egr-1), or differentiation (eg, myocardin).^4–6 Is it possible, or even plausible, from a cellular standpoint, that a single transcription factor could potentially play an important part in all 3 of these processes?

	Krüppel Complexity

 
The Krüppel-like family of transcription factors contain zinc finger DNA binding domains and presently include at least 16 mammalian members,⁷ with several having important roles in cardiovascular pathophysiology.⁸ One might think that there would be redundancy among so many family members; however, the non–zinc finger domain of these transcription factors displays structural heterogeneity, resulting in surprising functional diversity among Krüppel proteins.⁹ In particular, the role of Krüppel-like factor (KLF)4 in vascular biology and the mechanisms of its effects are as complex as the cells that participate in vascular disease are diverse.

For example, in . . . [Full Text of this Article]

Related Article:

Conditional Deletion of Krüppel-Like Factor 4 Delays Downregulation of Smooth Muscle Cell Differentiation Markers but Accelerates Neointimal Formation Following Vascular Injury

Tadashi Yoshida, Klaus H. Kaestner, and Gary K. Owens
Circ. Res. 2008 102: 1548-1557. [Abstract] [Full Text] [PDF]

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				B. Zheng, M. Han, M. Bernier, X.-h. Zhang, F. Meng, S.-b. Miao, M. He, X.-m. Zhao, and J.-k. Wen Kruppel-like Factor 4 Inhibits Proliferation by Platelet-derived Growth Factor Receptor {beta}-mediated, Not by Retinoic Acid Receptor {alpha}-mediated, Phosphatidylinositol 3-Kinase and ERK Signaling in Vascular Smooth Muscle Cells J. Biol. Chem., August 21, 2009; 284(34): 22773 - 22785. [Abstract] [Full Text] [PDF]