Glomerular expression of transforming growth factor-β (TGF-β) isoforms in mice lacking CD2-associated protein

Robert P. Woroniecki, Mario Schiffer, Andrey S. Shaw, Frederick J. Kaskel, Erwin P. Bottinger

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Mice lacking CD2-associated protein (CD2AP-/-) develop glomerular lesions resembling human focal segmental glomerulosclerosis (FSGS) between 3-4 weeks of age and die approximately 2 weeks later from massive proteinuria and renal failure. The mechanisms involved in the glomerular injury in this model are unclear. In this study, we used laser capture microdissection (LCM) and real-time PCR, and examined expression of TGF-β isoforms in CD2AP-/- mice at the level of isolated glomeruli. Total RNA yield from cryosections of 30 glomeruli was 10.71 ng (SD, 5.45) in CD2AP+/+ group (n=7), and 4.20 ng (SD, 2.04) in CD2AP-/- group (n=8), p=0.008. Expression of TGF-β1 mRNA was increased 1.5-fold in the whole kidney (p=0.030), and twofold in isolated CD2AP-/- glomeruli (p=0.026). Whole kidney mRNA of TGF-β receptor I (RI) and II (RII) was not different in CD2AP-/- and CD2AP+/+ animals, but it was increased in CD2AP-/- glomerular samples by 4.38-fold (p=0.001) and 11.37-fold (p=0.0163), respectively. By using LCM we confirmed increased glomerular expression levels of TGF-β isoforms previously described by our group in glomeruli isolated by sieving in CD2AP KO mice and underscored the importance of local factors in the development of glomerulosclerosis.

Original languageEnglish (US)
Pages (from-to)333-338
Number of pages6
JournalPediatric Nephrology
Volume21
Issue number3
DOIs
StatePublished - Mar 2006

Keywords

  • Laser capture
  • Microgenomics
  • TGF-β signaling

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

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