Tubulointerstitial nephritis antigen: an extracellular matrix protein that selectively regulates tubulogenesis vs. glomerulogenesis during mammalian renal development.
Tubulointerstitial nephritis antigen (TIN-ag) is an extracellular matrix protein and 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 approximately 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.
Kanwar
Y S
YS
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611, USA. y-kanwar@nwu.edu
Kumar
A
A
Yang
Q
Q
Tian
Y
Y
Wada
J
J
Kashihara
N
N
Wallner
E I
EI
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D018076:DNA, Complementary / Q000032:analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007678:Kidney Glomerulus / Q000196:embryology*; D007684:Kidney Tubules / Q000196:embryology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009395:Nephritis, Interstitial / Q000276:immunology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D034501:Telomere-Binding Proteins
D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D016326:Extracellular Matrix Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D034501:Telomere-Binding Proteins; C490058:Tinag protein, mouse; C499083:Tinf2 protein, mouse; D017027:Protein Tyrosine Phosphatases; C516890:Ptpro protein, mouse; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3