Absence of the lysosomal protein Limp-2 attenuates renal injury in crescentic glomerulonephritis View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2014-05

AUTHORS

Darren Hiu Kwong Lee, Poh-Yi Gan, Marina Katerelos, Scott Andrew Fraser, Kurt Gleich, Stephen Roger Holdsworth, David Anthony Power

ABSTRACT

In humans, mutations of the intrinsic lysosomal protein SCARB2 are associated with myoclonic epilepsy, collapsing focal and segmental glomerulosclerosis, and tubular proteinuria. Mice with deficiency of Limp-2 (the murine homologue) develop tubular proteinuria but not focal and segmental glomerulosclerosis and they have a defect in macrophage function. To further elucidate the role of Limp-2 in immune function, we induced anti-glomerular basement membrane (GBM) model of crescentic glomerulonephritis in wild-type (WT) and Limp-2(-/-) littermates by intraperitoneal injections of nephrotoxic sheep serum. Renal injury and immune responses were assessed on day 14. Compared with WT, Limp-2(-/-) mice had significantly reduced crescent formation, interstitial inflammation and a trend to reduced tubulointerstitial injury. On day 1 during the heterologous phase of the disease, albuminuria was significantly increased in WT but not in Limp-2(-/-) mice. On day 14, albuminuria and renal function were similar in the two groups. There was, however, a significant reduction in the influx of glomerular macrophages and CD4(+) T cells in Limp-2(-/-) mice. Interleukin (IL)-4 and macrophage chemoattractant protein-1 (MCP-1) mRNA expression levels were significantly reduced. Despite the reduction in numbers of infiltrating cells, flow cytometry showed no difference in macrophage or T-cell numbers in the peripheral blood from untreated mice. The systemic humoral immune response, determined by glomerular mouse immunoglobulin G (IgG) deposition and mouse anti-sheep IgG subclass production, was similar in both groups. These data suggest that absence of Limp-2 reduces inflammation in experimental crescentic glomerulonephritis with decreased macrophage and T-cell infiltration in the kidney. It suggests an important role for Limp-2 in mediating the inflammatory response. More... »

PAGES

400

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/icb.2013.104

DOI

http://dx.doi.org/10.1038/icb.2013.104

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1001333670

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24394995


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This table displays all metadata directly associated to this object as RDF triples.

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