Autocrine class 3 semaphorin system regulates slit diaphragm proteins and podocyte survival

Fangxia Guan, G. Villegas, J. Teichman, P. Mundel, A. Tufro

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Class 3 semaphorins are guidance proteins that play crucial roles during development. Semaphorins 3A (sema 3A) and 3F are expressed by podocytes in vivo throughout ontogeny and their function is unknown. Here we examined the expression of class 3 semaphorins (3A, 3B, 3C, 3D, 3E, and 3F) and their receptors (neuropilins 1 and 2, plexins A1, A2, A3, B2, and D1) in undifferentiated and differentiated mouse podocytes using reverse transcriptase-polymerase chain reaction (RT-PCR). All class 3 semaphorins, neuropilins 1 and 2 are expressed by undifferentiated and differentiated podocytes at similar levels. Differentiated podocytes expressed 2-4-fold higher plexin A1, A2, and A3 mRNA levels than undifferentiated podocytes. To examine semaphorin regulation, we exposed podocytes to recombinant sema 3A. Sema 3A decreased semaphorin 3B, plexin A1, A3, and D1 ≥50% and reduced plexin A2 mRNA to undetectable levels. To identify sema 3A function in podocytes, we examined whether sema 3A regulates slit diaphragm proteins and podocyte survival. Sema 3A induced a dose-response podocin downregulation and decreased its interaction with CD2-associated protein and nephrin, as determined by Western analysis and co-immunoprecipitation. To evaluate sema 3A role in podocyte survival, we quantified podocyte apoptosis using a caspase 3 activity marker. Sema 3A induced a 10-fold increase in podocyte apoptosis and significantly decreased the activity of the Akt survival pathway. Our data indicate that (1) immortalized podocytes in culture have a functional autocrine semaphorin system that is regulated by differentiation and ligand availability; (2) sema 3A signaling regulates the expression and interactions of slit-diaphragm proteins and decreases podocyte survival.

Original languageEnglish (US)
Pages (from-to)1564-1569
Number of pages6
JournalKidney International
Volume69
Issue number9
DOIs
StatePublished - May 2006

Fingerprint

Semaphorins
Podocytes
Diaphragm
Semaphorin-3A
Proteins
Neuropilin-2
Neuropilin-1
varespladib methyl
Apoptosis
Messenger RNA
Reverse Transcriptase Polymerase Chain Reaction
Immunoprecipitation
Caspase 3

Keywords

  • Apoptosis
  • CD2AP
  • Podocin nephrin
  • Podocyte
  • Semaphorin 3A

ASJC Scopus subject areas

  • Nephrology

Cite this

Autocrine class 3 semaphorin system regulates slit diaphragm proteins and podocyte survival. / Guan, Fangxia; Villegas, G.; Teichman, J.; Mundel, P.; Tufro, A.

In: Kidney International, Vol. 69, No. 9, 05.2006, p. 1564-1569.

Research output: Contribution to journalArticle

Guan, F, Villegas, G, Teichman, J, Mundel, P & Tufro, A 2006, 'Autocrine class 3 semaphorin system regulates slit diaphragm proteins and podocyte survival', Kidney International, vol. 69, no. 9, pp. 1564-1569. https://doi.org/10.1038/sj.ki.5000313
Guan, Fangxia ; Villegas, G. ; Teichman, J. ; Mundel, P. ; Tufro, A. / Autocrine class 3 semaphorin system regulates slit diaphragm proteins and podocyte survival. In: Kidney International. 2006 ; Vol. 69, No. 9. pp. 1564-1569.
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