Tubulointerstitial nephritis antigen: An extracellular matrix protein that selectively regulates tubulogenesis vs. glomerulogenesis during mammalian renal development

Yashpal S. Kanwar, Anil Kumar, Qiwei Yang, Yufeng Tian, Jun Wada, Naoki Kashihara, Elisabeth I. Wallner

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31 Citations (Scopus)

Abstract

Tubulointerstitial nephritis antigen (TIN-ag) is an extracellular matrix protein find is expressed in the renal tubular basement membranes. Its role in metanephric development was investigated. TIN-ag cDNA, isolated from the newborn mouse library, had an ORF of 1,425 nucleotides, a putative signal sequence, and an ATP/GTP-binding site. The translated sequence had ≃80% identity with rabbit TIN-ag. Among various tissues, TIN-ag mRNA was primarily expressed in the newborn kidney. In the embryonic metanephros, TIN-ag expression was confined to the distal convolution or pole of the S-shaped body, the segment of the nascent nephron that is the progenitor of renal tubules. Treatment with TIN-ag antisense oligodeoxynucleotide induced dysmorphogenesis of the embryonic metanephroi, malformation of the S-shaped body, and a decrease in the tubular population, whereas the glomeruli were unaffected. Treatment also led to a decrease of TIN-Ag mRNA, de novo synthesis of TIN-ag protein, and its antibody reactivity. The mRNA expression of glomerular epithelial protein 1 (a marker for renal podocytes), anti- heparan-sulfate-proteoglycan antibody reactivity, and wheat germ agglutinin lectin staining of the metanephros were unaffected. The anti-TIN-ag antibody treatment also caused deformation of the S-shaped body and a reduction in the tubular population, whereas the glomeruli were unchanged. The data suggest that the TIN-ag, unlike other basement membrane proteins, selectively regulates tubulogenesis, whereas glomerulogenesis is largely unaffected.

Original languageEnglish
Pages (from-to)11323-11328
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number20
DOIs
Publication statusPublished - Sep 28 1999
Externally publishedYes

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Keywords

  • Metanephric development

ASJC Scopus subject areas

  • Genetics
  • General

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