This Article Full Text Full Text (PDF) All Versions of this Article: jhc.2009.953224v1 57/7/623    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Turk, T. Articles by Goldschmeding, R. Search for Related Content PubMed PubMed Citation Articles by Turk, T. Articles by Goldschmeding, R. Social Bookmarking                         What's this?

BMP Signaling and Podocyte Markers Are Decreased in Human Diabetic Nephropathy in Association With CTGF Overexpression

Tamara Turk¹, Jan Willem Leeuwis¹, Julia Gray, Suzy V. Torti, Karen M. Lyons, Tri Q. Nguyen and Roel Goldschmeding

Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands (TT,JWL,TQN,RG); Department of Internal Medicine, Clinical Hospital Center Rijeka, Rijeka, Croatia (TT); FibroGen, Inc., San Francisco, California (JG); Department of Biochemistry and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina (SVT); and University of California Los Angeles, Los Angeles, California (KML)

Correspondence to: Roel Goldschmeding, Department of Pathology, H04.312, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. E-mail: r.goldschmeding{at}umcutrecht.nl

Diabetic nephropathy is characterized by decreased expression of bone morphogenetic protein-7 (BMP-7) and decreased podocyte number and differentiation. Extracellular antagonists such as connective tissue growth factor (CTGF; CCN-2) and sclerostin domain-containing-1 (SOSTDC1; USAG-1) are important determinants of BMP signaling activity in glomeruli. We studied BMP signaling activity in glomeruli from diabetic patients and non-diabetic individuals and from control and diabetic CTGF^+/+ and CTGF^+/– mice. BMP signaling activity was visualized by phosphorylated Smad1, -5, and -8 (pSmad1/5/8) immunostaining, and related to expression of CTGF, SOSTDC1, and the podocyte differentiation markers WT1, synaptopodin, and nephrin. In control and diabetic glomeruli, pSmad1/5/8 was mainly localized in podocytes, but both number of positive cells and staining intensity were decreased in diabetes. Nephrin and synaptopodin were decreased in diabetic glomeruli. Decrease of pSmad1/5/8 was only partially explained by decrease in podocyte number. SOSTDC1 and CTGF were expressed exclusively in podocytes. In diabetic glomeruli, SOSTDC1 decreased in parallel with podocyte number, whereas CTGF was strongly increased. In diabetic CTGF^+/– mice, pSmad1/5/8 was preserved, compared with diabetic CTGF^+/+ mice. In conclusion, in human diabetic nephropathy, BMP signaling activity is diminished, together with reduction of podocyte markers. This might relate to concomitant overexpression of CTGF but not SOSTDC1. (J Histochem Cytochem 57:623–631, 2009)

Key Words: kidney • bone morphogenetic proteins • Smads • connective tissue growth factor • diabetic nephropathy • glomerulus • podocytes • quantitative histochemistry

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Guidelines | Subscriptions | About | exPRESS - Current - Archive | Business Information | Contact

The Journal of Histochemistry & Cytochemistry is owned, published, and licensed by The Histochemical Society © 2009