Localization of TGF-beta signaling intermediates Smad2, 3, 4, and 7 in developing and mature human and mouse kidney

J Histochem Cytochem. 2007 Mar;55(3):275-85. doi: 10.1369/jhc.6A7083.2006. Epub 2006 Dec 1.


Smad proteins are signaling intermediates of the TGF-beta superfamily and 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. 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 was remarkable. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Blotting, Western
  • Humans
  • Immunohistochemistry
  • Kidney / embryology
  • Kidney / growth & development
  • Kidney / metabolism*
  • Mice
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Smad2 Protein / metabolism*
  • Smad3 Protein / metabolism*
  • Smad4 Protein / metabolism*
  • Smad7 Protein / metabolism*
  • Species Specificity
  • Transforming Growth Factor beta / physiology*


  • Smad2 Protein
  • Smad3 Protein
  • Smad4 Protein
  • Smad7 Protein
  • Transforming Growth Factor beta