CD44 Deficiency Increases Tubular Damage But Reduces Renal Fibrosis in Obstructive Nephropathy

Rouschop, Kasper M.A.; Sewnath, Miguel E.; Claessen, Nike; Roelofs, Joris J. T. H.; Hoedemaeker, Inge; Neut, Ronald van der; Aten, Jan; Pals, Steven T.; Weening, Jan J.; Florquin, Sandrine

doi:10.1097/01.asn.0000115703.30835.96

Cited by 103 publications

(129 citation statements)

References 50 publications

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“…44 However, little information about E-selectin is available. Because Bsg acts as an E-selectin ligand on inflammatory cells, 34 we next examined E-selectin expression in the kidney.…”

Section: Macrophage Infiltration Is Lower In Bsg ϫ/ϫ Micementioning

confidence: 99%

Basigin/CD147 Promotes Renal Fibrosis after Unilateral Ureteral Obstruction

Kato

Kosugi

Sato

et al. 2011

The American Journal of Pathology

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Regardless of their primary causes, progressive renal fibrosis and tubular atrophy are the main predictors of progression to end-stage renal disease. Basigin/ CD147 is a multifunctional molecule-it induces matrix metalloproteinases and hyaluronan, for example-and has been implicated in organ fibrosis. However, the relationship between basigin and organ fibrosis has been poorly studied. We investigated basigin's role in renal fibrosis using a unilateral ureteral obstruction model. Basigin-deficient mice (Bsg ؊/؊ ) demonstrated significantly less fibrosis after surgery than Bsg ؉/؉ mice. Fewer macrophages had infiltrated in Bsg ؊/؊ kidneys. Consistent with these in vivo data, primary cultured tubular epithelial cells from Bsg ؊/؊ mice produced less matrix metalloproteinase and exhibited less motility on stimulation with transforming growth factor ␤. Furthermore, Bsg ؊/؊ embryonic fibro blasts produced less hyaluronan and ␣-smooth muscle actin after transforming growth factor ␤ stimulation. Together, these results demonstrate for the first time that basigin is a key regulator of renal fibrosis. Basigin could be a candidate target molecule for the prevention of organ fibrosis.

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“…44 However, little information about E-selectin is available. Because Bsg acts as an E-selectin ligand on inflammatory cells, 34 we next examined E-selectin expression in the kidney.…”

Section: Macrophage Infiltration Is Lower In Bsg ϫ/ϫ Micementioning

confidence: 99%

Basigin/CD147 Promotes Renal Fibrosis after Unilateral Ureteral Obstruction

Kato

Kosugi

Sato

et al. 2011

The American Journal of Pathology

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“…However, upon injury CD44 is rapidly up-regulated at the cell surface of TECs (7)(8)(9)(10)(11)(12)(13). The strategic position of CD44 on the urinary mucosal surface raises the possibility that this molecule may play a role during UTI.…”

mentioning

confidence: 98%

“…Immunohistochemical staining was performed using specific Abs directed against: CD44 (clone IM7.8.1; ATCC), neutrophils (Ly-6G, (GR-1); BD Pharmingen), and HA (biotinylated HA binding protein; Calbiochem)), as previously described (12,13). As a negative control we used species and isotype-matched Abs (BD Pharmingen).…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…MIP-2, keratinocyte-derived chemokine (KC/Gro-␣), IL-1␤ (all R&D Systems), and mouse MPO (HyCult Biotechnology) were measured in renal homogenates as previously described (13) by specific ELISAs according to the manufacturer's instructions. Protein concentrations of the renal homogenates were determined using a Bradford protein assay (Bio-Rad).…”

Section: Cytokine Chemokine and Myeloperoxidase (Mpo) Elisasmentioning

confidence: 99%

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Urothelial CD44 Facilitates Escherichia coli Infection of the Murine Urinary Tract

Rouschop¹,

Sylva²,

Teske³

et al. 2006

The Journal of Immunology

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Escherichia coli is the most common pathogen found in urinary tract infections (UTIs), mainly affecting children and women. We report that CD44, a hyaluronic acid (HA) binding protein that mediates cell-cell and cell-matrix interactions, facilitates the interaction of E. coli with urothelial cells and thus the infection of the host. We found that CD44 is constitutively expressed on urothelial cells and that HA accumulates in E. coli-induced UTI. In CD44-deficient mice, the bacterial outgrowth was dramatically less compared with wild-type mice despite similar granulocyte influx in the bladder and in the kidney as well as comparable cytokines/chemokines levels in both genotypes. E. coli was able to bind HA, which adhered to CD44-positive tubular epithelial cells. Most importantly, the interaction of CD44 on tubular epithelial cells with HA facilitated the migration of E. coli through the epithelial monolayer. The results provide evidence that CD44 on urothelial cells facilitates E. coli UTI. Disruption of the interaction between CD44 and HA in the bladder may provide a new approach to prevent and to treat UTI.

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“…We did not find reports ofVCAMl induction in other animal models ofDN. CD44 is induced in kidneys injured by ischemia [96] or autoimmunity [97] and CD44 contributes to renal neutrophil and macrophage infiltration [98]. Induction of CD44 has not been reported in diabetic kidneys and CD44 is not induced in proximal tubule cell lines by high glucose [99].…”

mentioning

confidence: 99%

Adriamycin nephrotoxicity is reduced by metallothionein over-expression and kidney gene expression is modified by diabetes in the OVE26 diabetic model.

Yang¹

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Yang, Lu, "Adriamycin nephrotoxicity is reduced by metallothionein over-expression and kidney gene expression is modified by diabetes in the OVE26 diabetic model." (2010 This thesis is divided into two parts below.Part I Adriamycin (ADR) can produce nephrotoxicity in rodents. The underlying mechanism may relate to ADR induced oxidative stress. In this study, we used transgenic mice (NMT3), which over-expressed the antioxidant protein metallothionein (MT) in podocytes, to study MT's protective potential on ADR nephrotoxicity. Urine and kidney samples were collected from control and transgenic mice at multiple time points after ADR injection, whose results showed that MT transgene alleviated ADR damage by reducing albuminuria, decreasing podocyte loss and protecting podocyte ultra-structure.Part II OVE26 mice are a good model of severe diabetic nephropathy (DN). We examined progressive changes in renal gene and protein expression in OVE26 and control mice.Inflammatory genes were most affected by diabetes, especially at oldest ages tested, iv which correlated with increasingly severe albuminuria. Vitamin D metabolism was also changed by DN.

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CD44 Deficiency Increases Tubular Damage But Reduces Renal Fibrosis in Obstructive Nephropathy

Cited by 103 publications

References 50 publications

Basigin/CD147 Promotes Renal Fibrosis after Unilateral Ureteral Obstruction

Basigin/CD147 Promotes Renal Fibrosis after Unilateral Ureteral Obstruction

Urothelial CD44 Facilitates Escherichia coli Infection of the Murine Urinary Tract

Adriamycin nephrotoxicity is reduced by metallothionein over-expression and kidney gene expression is modified by diabetes in the OVE26 diabetic model.

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