Tubulointerstitial nephritis antigen: An extracellular matrix protein thatselectively regulates tubulogenesis vs. glomerulogenesis during mammalian renal development
Ys. Kanwar et al., Tubulointerstitial nephritis antigen: An extracellular matrix protein thatselectively regulates tubulogenesis vs. glomerulogenesis during mammalian renal development, P NAS US, 96(20), 1999, pp. 11323-11328
Citations number
19
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Tubulointerstitial nephritis antigen (TIN-ag) is an extracellular matrix pr
otein and is expressed in the renal tubular basement membranes. Its role in
metanephric development was investigated. TIN-ag cDNA, isolated from the n
ewborn mouse library, had an ORF of 1,425 nucleotides, a putative signal se
quence, and an ATP/GTP-binding site. The translated sequence had approximat
e to 80% identity with rabbit TIN-ag. Among various tissues, TIN-ag mRNA wa
s 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 r
enal 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 synth
esis of TIN-ag protein, and its antibody reactivity. The mRNA expression of
glomerular epithelial protein 1 (a marker for renal podocytes), anti-hepar
an-sulfate-proteoglycan antibody reactivity, and wheat germ agglutinin lect
in staining of the metanephros were unaffected. The anti-TIN-ag antibody tr
eatment 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 regu
lates tubulogenesis, whereas glomerulogenesis is largely unaffected.