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

Research output: Contribution to journalArticle

31 Citations (Scopus)


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
Issue number20
Publication statusPublished - Sep 28 1999
Externally publishedYes



  • Metanephric development

ASJC Scopus subject areas

  • Genetics
  • General

Cite this