Sidekick-1 is upregulated in glomeruli in HIV-associated nephropathy.
Infection of podocytes by HIV-1 induces unique changes in phenotype, which contribute to the pathogenesis of glomerular disease in HIV-associated nephropathy (HIVAN). The host genetic pathways altered by HIV-1 infection that are responsible for these phenotypic changes are largely unknown. For identifying such pathways, representational difference analysis was performed comparing cDNA from HIV-1 transgenic podocytes with nontransgenic controls. In this way, a gene named sidekick-1 (sdk-1) was cloned, a transmembrane protein of the Ig superfamily that is highly upregulated in HIV-1 transgenic podocytes. Sdk-1 and its ortholog, sidekick-2 (sdk-2), were recently shown to guide axonal terminals to specific synapses in developing neurons. Their presence and role in other organs, including the kidney, has not been described. The current study demonstrates developmental expression of both sdk-1 and sdk-2 and a tight spatial and temporal regulation of these genes in kidney. During nephrogenesis, sidekick expression was observed first in ureteric bud and ureteric bud-derived tissues in a pattern similar to other genes known to play important roles in branching morphogenesis. In adult murine renal tissue, sidekick proteins were seen in glomeruli at low levels, and expression of sdk-1 was greatly upregulated in diseased HIV-1 transgenic mouse kidneys. In a human HIVAN kidney biopsy, sidekick expression was increased in glomeruli in a pattern consistent with the mouse model. It is proposed that the dysregulation of sdk-1 protein may play an important role in HIVAN pathogenesis.
Kaufman
Lewis
L
Department of Medicine, Division of Nephrology, Mount Sinai School of Medicine, New York, New York 10029, USA. lewis.kaufman@mssm.edu
Hayashi
Kayo
K
Ross
Michael J
MJ
Ross
Michael D
MD
Klotman
Paul E
PE
D016263:AIDS-Associated Nephropathy / Q000473:pathology*; D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism; D015152:Blotting, Northern; D015815:Cell Adhesion Molecules; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D012313:RNA / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014018:Tissue Distribution; D019076:Transgenes; D015854:Up-Regulation; D014513:Ureter / Q000196:embryology
D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D007074:Immunoglobulin G; D008565:Membrane Proteins; C493091:SDK1 protein, human; C493090:sidekick-1 protein, mouse; D012313:RNA