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JHC exPRESS: First Published December 1, 2006. doi:10.1369/jhc.6A7083.2006
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A more recent version of this article appeared on March 1, 2007.
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Localization of TGF-beta Signaling Intermediates Smad2, -3, -4, and -7 in Developing and Mature Human and Mouse Kidney

Miriam C. Banas 1*, W. Tony Parks 1, Kelly L. Hudkins 1, Bernhard Banas 1, Matthew Holdren 1, Masayuki Iyoda 1, Tomasz A. Wietecha 1, Jolanta Kowalewska 1, Gang Liu 1 and Charles E. Alpers 1

1 Department of Pathology, University of Washington, Seattle, Washington (MCB,WTP,KLH,MH,MI,TAW,JK,GL,CEA), and Klinik und Poliklinik für Innere Medizin II, University of Regensburg, Regensburg, Germany (MCB,BB)

* To whom correspondence should be addressed. E-mail: banas{at}gmx.de .

Submitted on August 18, 2006
Accepted on 13 November 2006


   Abstract
Smad proteins are signaling intermediates of the TGF-{beta} superfamily, which are involved in a range of biological activities including development and immune responses. We studied the expression of TGF-{beta}-receptor activated Smads (Smad2 and Smad3), the common partner Smad (Smad4), an inhibitory Smad (Smad7) and the activated (phosphorylated) Smad2 (pSmad2) in developing and adult kidneys of humans and mice. These studies demonstrate associated expression of these Smads in multiple renal cell types in all developmental stages and in mature non-diseased kidneys. Smad expression is in general most widespread at the earliest stages of nephron development and diminishes as components of the nephrons become more differentiated. Remarkable was the paucity of Smad expression in mesangial cells in contrast to widespread expression of these Smads in glomerular visceral epithelial cells in both developing and mature kidneys. Divergent and less extensive expression of Smad4, compared with other Smad proteins, was also demonstrated in tubules of human kidneys. Based on the observed expression patterns, these findings demonstrate for the first time expression of the TGF-{beta}-receptor activated Smad2 and Smad3, the common mediator Smad4 and the inhibitory Smad7 in the developing human fetal kidney, extending observations previously made in rodent systems to humans.

Key Words: Smads, TGF beta, renal pathology, kidney development, cell signaling, immunohistochemistry


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