Podocan, a novel small leucine-rich repeat protein expressed in the sclerotic glomerular lesion of experimental HIV-associated nephropathy.
Growing evidence suggests that human immunodeficiency virus (HIV)-1 infection of podocytes plays a central role in the glomerular disease of HIV-associated nephropathy (HIVAN). As an approach to identify host genes involved in the pathogenesis of the sclerotic glomerular lesion in HIVAN, representational difference analysis of cDNA was used to identify differentially expressed genes in HIV-1 transgenic and nontransgenic podocytes. We isolated a novel member of the small leucine-rich repeat (SLR) protein family, podocan, that is expressed at high levels in the HIV-1 transgenic podocytes. In normal embryonic kidney, a 3.2-kb podocan transcript was detected at low levels, and expression increased dramatically within 24 h following birth. Expression of a 2.3-kb transcript became evident after birth and gradually increased to 50% of the total podocan RNA in the mature kidney. Phylogenetically, podocan represents a new class in the SLR protein gene family, an expanding protein family sharing homology with the small leucine-rich repeat proteoglycans. The 3.2-kb transcript encodes a predicted 611-amino acid secretory protein with 20 leucine-rich repeats, a unique N-terminal cysteine-rich cluster pattern and a highly acidic C-terminal domain. In situ hybridization of normal kidney revealed podocan mRNA expression in podocytes and likely vascular endothelial cells within the glomerulus. The immunohistochemical staining pattern of podocan protein in normal kidney glomeruli was consistent with that of the glomerular basement membrane, and staining was markedly increased in sclerotic glomerular lesions in the transgenic HIVAN model. Thus, podocan defines a new class within the SLR protein family and is a previously unrecognized component of the sclerotic glomerular lesion that develops in the course of experimental HIVAN.
Ross
Michael D
MD
Department of Medicine, Divisions of Nephrology and Infectious Diseases, Mount Sinai School of Medicine, New York, New York 10029, USA. michael.d.ross@mssm.edu
Bruggeman
Leslie A
LA
Hanss
Basil
B
Sunamoto
Masaaki
M
Marras
Daniele
D
Klotman
Mary E
ME
Klotman
Paul E
PE
D016263:AIDS-Associated Nephropathy / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D006023:Glycoproteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D007668:Kidney / Q000378:metabolism; D007678:Kidney Glomerulus / Q000473:pathology*; D007930:Leucine / Q000737:chemistry; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010802:Phylogeny; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D019076:Transgenes
D018076:DNA, Complementary; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C477527:PODN protein, human; D011506:Proteins; D012333:RNA, Messenger; C477528:podocan protein, mouse; D012313:RNA; D007930:Leucine