Sidekick-1 Is Upregulated in Glomeruli in HIV-Associated Nephropathy

Kaufman, Lewis; Hayashi, Kamichika; Ross, Michael J.; Klotman, Paul E.

doi:10.1097/01.asn.0000128975.28958.c2

Cited by 38 publications

(32 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Normally, it is not identified in adult podocytes; however, in the setting of HIV-1 transgene expression, the protein is highly upregulated [26]. Sdk-1 and its ortholog, sidekick-2 (Sdk-2) function as homophilic binding proteins that regulate cell-cell adhesion [28].…”

Section: Podocyte Response To Viral Infectionmentioning

confidence: 99%

See 1 more Smart Citation

Podocytes in HIV-Associated Nephropathy

Klotman³

2007

Nephron Clin Pract

View full text Add to dashboard Cite

HIV-associated nephropathy (HIVAN) is the leading cause of end-stage renal failure in HIV-1 seropositive patients. The pathologic findings include collapsing focal segmental glomerulosclerosis with proliferation of epithelial cells in Bowman’s space. Anatomically, these cells correspond to podocytes and exhibit a unique phenotype with loss of many differentiation markers including synaptopodin and dysregulation of the cell cycle markers consistent with proliferation. Podocyte dysfunction appears to be a direct result of HIV-1 protein expression, specifically Nef and Vpr as well as specific host factors that have yet to be elucidated. The mechanism by which Nef induces podocyte proliferation and dedifferentiation has been traced to its ability to activate several signaling pathways including Src-Stat3 and ras-raf-MAPK1, 2. Activation of the cAMP/PKA pathway with all-trans-retinoic acid appears to modulate these changes and returns podocytes to a differentiated, nonproliferating phenotype.

show abstract

Section: Podocyte Response To Viral Infectionmentioning

confidence: 99%

“…To delineate these factors, representational difference analysis (RDA) of cDNA obtained from HIV-1 podocytes was compared to wild-type podocytes. Two novel proteins, sidekick-1 (Sdk-1) and podocan were identified by this method [26, 27]. …”

Section: Podocyte Response To Viral Infectionmentioning

confidence: 99%

Podocytes in HIV-Associated Nephropathy

Klotman³

2007

Nephron Clin Pract

View full text Add to dashboard Cite

show abstract

“…On chromosome 7, the genes located the most closely to the breakpoint are SDK1 and CARD11. SDK1 was shown to be involved in synaptic adhesion during the development of the retina [Yamagata et al, 2002] and in the pathogenesis of HIVassociated nephropathy [Kaufman et al, 2004]. We cannot rule out the possibility that this gene is implicated in the phenotype.…”

Section: Discussionmentioning

confidence: 92%

Truncation ofNHEJ1 in a patient with polymicrogyria

et al. 2007

View full text Add to dashboard Cite

Polymicrogyria (PMG) is a common malformation of the human cerebral cortex for which both acquired and genetic causes are known. Although genetic heterogeneity is documented, only one gene is currently known to cause isolated PMG. To clone new genes involved in this type of cerebral malformation, we studied a fetus presenting a defect of cortical organization consisting of a polymicrogyric cortex and neuronal heterotopia within the white matter. Karyotype analysis revealed that the fetus was carrier of a balanced, de novo, chromosomal translocation t(2;7)(q35;p22). Cloning and sequencing of the two translocation breakpoints reveals that the chromosomal rearrangement disrupts the coding region of a single gene, called NHEJ1, Cernunnos, or XLF, in 2q35. The NHEJ1 gene was recently identified as being responsible for autosomal recessive immunodeficiency with microcephaly. Using quantitative PCR experiments, we show that a truncated transcript is expressed in the polymicrogyric patient cells, suggesting a potential dominant negative effect possibly leading to a different phenotype. We performed in situ hybridization on human embryos and showed that the NHEJ1 transcript is preferentially expressed in the telencephalic ventricular and subventricular zones, consistent with the phenotype of the affected individual. In the human adult central nervous system (CNS), NHEJ1 is mainly expressed in the cerebral cortex and in the cerebellum. The association of PMG with the disruption of its transcript suggests that, in addition to its recently uncovered function in the immune system, the NHEJ1 protein may also play a role during development of the human cerebral cortex.

show abstract

“…Using this approach, the small leucine-rich repeat protein Podocan and the homophilic adhesion molecule Sidekick-1 were found to be upregulated in podocytes in HIVAN [36,37]. The role of these proteins in HIVAN pathogenesis has yet to be fully defined.…”

Section: Podocyte-specific Candidate Genesmentioning

confidence: 99%

Gene candidates in HIV-associated nephropathy

Ross¹

2006

Expert Review of Clinical Immunology

View full text Add to dashboard Cite

Sidekick-1 Is Upregulated in Glomeruli in HIV-Associated Nephropathy

Cited by 38 publications

References 23 publications

Podocytes in HIV-Associated Nephropathy

Podocytes in HIV-Associated Nephropathy

Truncation ofNHEJ1 in a patient with polymicrogyria

Gene candidates in HIV-associated nephropathy

Contact Info

Product

Resources

About