Vasodilator-Stimulated Phosphoprotein–Deficient Mice Demonstrate Increased Platelet Activation but Improved Renal Endothelial Preservation and Regeneration in Passive Nephrotoxic Nephritis

Hohenstein, Bernd; Kasperek, Laura; Kobelt, Dieter-Johannes; Daniel, Christoph; Gambaryan, Stepan; Renné, Thomas; Walter, Ulrich; Amann, Kerstin; Hugo, Christian

doi:10.1681/asn.2004070591

Cited by 25 publications

(24 citation statements)

References 45 publications

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“…Moreover, a study on the association of VASP with nephritis was reported by Hohenstein et al (2005) who showed that VASP deficient mice were protected from long-term progression of nephro- .300 a Twelve single nucleotide polymorphisms (SNPs) of ENAH are shown, which were genotyped from ENAH in 178 patients with IgAN from the Kyung Hee medical center, Seoul, Korea and 397 control subjects; rs2039620, rs12034829, rs3795443 and rs1771316 showed statistically significant differences. Genotype distributions are shown as the number (%), odds ratio (OR), 95% confidence interval (CI), and P values were determined by logistic regression analysis with codominant, dominant, and recessive models controlling for gender as covariates.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the action of integrins on actin-rearrangement is known to be involved in the regulation of cellular differentiation, proliferation and survival , and in the leukocyte trafficking that is critical for immune surveillance and contributes to the pathogenesis of inflammatory and autoimmune diseases (Rose, 2006). Besides, ENAH is likely associated with the progression of glomerulonephritis as shown in a study on VASP (Hohenstein et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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The enabled homolog gene polymorphisms are associated with susceptibility and progression of childhood IgA nephropathy

et al. 2009

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The enabled homolog gene (ENAH, hMena) is abundantly expressed in mesangial tissue, and might play an important role in inflammatory processes of IgA nephropathy (IgAN). The present study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) of the ENAH and childhood IgAN. We analyzed 12 SNPs of ENAH in 176 patients with childhood IgAN and 397 healthy controls. In addition, IgAN patients were dichotomized and compared with respect to several clinical and pathological parameters. Genotyping data showed significant differences between IgAN patients and controls in the frequency of rs2039620, rs12034829, and rs3795443. On comparison of patients with proteinuria to those without proteinuria (≤ or ＞ 4 mg/m 2 /h), rs12043633 was significantly different between the two groups. With regard to maximum proteinuria (≤ or ＞ 4 mg/m 2 /h), rs3795443, rs4653643, rs6751, rs10799319, rs7555139, rs576861, and rs487591 showed significant allele frequency differences. For patients with and without gross hematuria, rs4653643, rs6751, rs10799319, rs7555139, rs576861, and rs487591 showed significant allele frequency differences. The rs3795443 was found to be associated with progression of pathological findings. Our results suggest that ENAH polymorphisms are associated with increased susceptibility, development of proteinuria and gross hematuria, and pathological progression of childhood IgAN.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The enabled homolog gene polymorphisms are associated with susceptibility and progression of childhood IgA nephropathy

et al. 2009

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“…Glomerulosclerosis was evaluated individually in at least 50 randomly selected glomeruli under ϫ400 magnification on periodic acidSchiff (PAS)-stained sections using a semiquantitative scoring system from 0 to 4 (0, normal glomeruli; 1, mesangial thickening of Ͻ25%; 2, mesangial proliferation and thickening up to 50%; 3, obliteration of capillaries and diffuse sclerosis up to 75%; and 4, complete capillary obliteration and thrombosis with global sclerosis up to 100%) (27,28). Values are given as score Ϯ SD per glomerular cross-section (gcs).…”

Section: Quantitative Analysis Of Immunostaining and Capillary Rarefamentioning

confidence: 99%

“…Glomerular capillary rarefaction was determined after staining for lectin from Lycopersicon esculentum (tomato). A semiquantitative scoring system from 0 to 3 was used (0, 0 to 25%; 1, 25 to 50%; 2, 50 to 75%; and 3, 75 to 100% loss of glomerular capillaries) (27 …”

Section: Quantitative Analysis Of Immunostaining and Capillary Rarefamentioning

confidence: 99%

P2Y1 Gene Deficiency Protects from Renal Disease Progression and Capillary Rarefaction during Passive Crescentic Glomerulonephritis

Hohenstein

Renk

Lang

et al. 2007

Journal of the American Society of Nephrology

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The metabotropic receptor P2Y1 is necessary for full ADP-induced platelet activation and is localized on various intrinsic renal cells, including mesangial cells, podocytes, and endothelial cells. To date, nothing is known about the role of the P2Y1 receptor during inflammatory renal disease. The role of the P2Y1 receptor was investigated using 22 P2Y1 gene-deficient (؊/؊) and 27 wild-type (wt) mice during the time course of passive crescentic nephrotoxic glomerulonephritis. Six P2Y1 ؊/؊ and six wt mice served as undiseased controls. Renal tissues were harvested on days 1, 10, and 28 after disease induction. No renal phenotype was found in P2Y1 ؊/؊ versus wt mice. In contrast, during crescentic glomerulonephritis, approximately 50% of all wt mice died, whereas all P2Y1 ؊/؊ mice survived. Renal function as assessed by creatinine clearance measurements, glomerulosclerosis, and tubulointerstitial injury indices as well as glomerular and interstitial matrix expansion were improved significantly in P2Y1 ؊/؊ compared with wt mice. These changes were preceded by reduced glomerular and peritubular capillary rarefaction indices in P2Y1 ؊/؊ compared with wt mice. The alteration of the rates of both peritubular apoptosis and endothelial cell proliferation suggests improved capillary preservation in P2Y1 ؊/؊ mice early in disease (day 10) and an additional enhanced repair reaction in P2Y1 ؊/؊ mice at the late time point (day 28), whereas injury on day 1 seemed to be equivalent in both groups. It is concluded that loss of P2Y1 receptor function safeguards against capillary loss, fibrosis, and death by renal failure during experimental crescentic glomerulonephritis.

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“…In addition to its role in normal cell growth (4,5), embryonic development (6) and homeostasis (7), VASP plays an essential role in many diseases, such as cancer metastasis (8,9), thrombosis (10), arteriosclerosis (11) and nephritis (12).…”

Section: Introductionmentioning

confidence: 99%

Vasodilator-stimulated phosphoprotein regulates osteosarcoma cell migration

Wei

et al. 2011

Oncol Rep

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Abstract. Vasodilator-stimulated phosphoprotein (VASP) has been reported to play an important role in the process of cell migration and tumor metastasis. However, to date, no study has examined VASP expression and its function in osteocarcoma cells. In this study, we analyzed the effect of VASP on osteosarcoma cell migration and the signal transduction pathways involved. We used two osteosarcoma cell strains (Mg-63 and Saos-2 cells) with different metastatic potential. Silencing of VASP gene expression was carried out using RNA interference in these cells. Knockdown of expression at the transcriptional or translational level was determined by RT-PCR or Western blot analysis, respectively. The metastatic potential of the tumor cells was determined by a wound healing migration assay. VASP mRNA expression was also determined in 30 human osteosarcoma samples. Furthermore, Rac1 was determined as a regulator of VASP function. RT-PCR and Western blotting showed that Mg-63 cells had a significantly higher VASP expression at both the transcriptional and translational levels compared to Saos-2 cells. The wound healing assay revealed that Mg-63 cells had more migratory potential compared to Saos-2 cells. The effect was found to be reversible when VASP was knocked down by siRNA in Mg-63 cells. Specimens from human patients with metastases had higher VASP expression compared to specimens of patients without metastases. Knockdown of Rac1 resulted in inhibition of VASP expression in sarcoma cells. These results suggest that VASP protein regulates osteosarcoma cell migration and metastasis. Rac1 and VASP interaction may be a potential target for osteosarcoma treatment. IntroductionOsteosarcoma is the most prevalent primary malignant bone tumor in children and young adults. Although the life expectancy of osteosarcoma patients has been prolonged due to improvement of neoadjuvant chemotherapy and surgical resection during the past three decades, the long-term survival and quality of life is still unsatisfactory. Poor outcome of osteosarcoma is mainly caused by metastatic disease, and previous studies have demonstrated that more than 30% of patients already display distant metastasis without clinical detectable signs at the time of diagnosis (1,2).Vasodilator-stimulated phosphoprotein (VASP), a member of the Ena/VASP family, has been implicated in regulating key cellular functions, such as shape change, adhesion and migration, which is mainly due to its ability to modify dynamic action cytoskeleton (3). In addition to its role in normal cell growth (4,5), embryonic development (6) and homeostasis (7), VASP plays an essential role in many diseases, such as cancer metastasis (8,9), thrombosis (10), arteriosclerosis (11) and nephritis (12).Expression of VASP has been reported to be dysregulated in several types of malignancies and is relevant to tumor metastasis. For example, its level was found to be significantly increased in lung adenocarcinomas and gastric carcinomas compared to normal tissue, and this increase was correlated wit...

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Vasodilator-Stimulated Phosphoprotein–Deficient Mice Demonstrate Increased Platelet Activation but Improved Renal Endothelial Preservation and Regeneration in Passive Nephrotoxic Nephritis

Cited by 25 publications

References 45 publications

The enabled homolog gene polymorphisms are associated with susceptibility and progression of childhood IgA nephropathy

The enabled homolog gene polymorphisms are associated with susceptibility and progression of childhood IgA nephropathy

P2Y1 Gene Deficiency Protects from Renal Disease Progression and Capillary Rarefaction during Passive Crescentic Glomerulonephritis

Vasodilator-stimulated phosphoprotein regulates osteosarcoma cell migration

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