Early detection of cysteine rich protein 61 (CYR61, CCN1) in urine following renal ischemic reperfusion injury

Muramatsu, Yasunari; Tsujie, Michiko; Kohda, Yukimasa; Pham, Bertha; Perantoni, Alan O.; Zhao, Hong; Jo, Sang-Kyung; Yuen, Peter S.T.; Craig, Leonard C.; Hu, Xiaobang; Star, Robert A.

doi:10.1046/j.1523-1755.2002.00633.x

Cited by 139 publications

(106 citation statements)

References 40 publications

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“…Also, CCN1/ CYR61 was induced in proximal straight tubules following ischemic reperfusion injury of the kidney (35). In the obstructed bladder, expression of CCN2/CTGF and CCN1/CYR61 were also induced (36).…”

Section: Discussionmentioning

confidence: 96%

Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment

Kawamura

Cheng

Suzuki³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

723

685

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Primary ovarian insufficiency (POI) and polycystic ovarian syndrome are ovarian diseases causing infertility. Although there is no effective treatment for POI, therapies for polycystic ovarian syndrome include ovarian wedge resection or laser drilling to induce follicle growth. Underlying mechanisms for these disruptive procedures are unclear. Here, we explored the role of the conserved Hippo signaling pathway that serves to maintain optimal size across organs and species. We found that fragmentation of murine ovaries promoted actin polymerization and disrupted ovarian Hippo signaling, leading to increased expression of downstream growth factors, promotion of follicle growth, and the generation of mature oocytes. In addition to elucidating mechanisms underlying follicle growth elicited by ovarian damage, we further demonstrated additive follicle growth when ovarian fragmentation was combined with Akt stimulator treatments. We then extended results to treatment of infertility in POI patients via disruption of Hippo signaling by fragmenting ovaries followed by Akt stimulator treatment and autografting. We successfully promoted follicle growth, retrieved mature oocytes, and performed in vitro fertilization. Following embryo transfer, a healthy baby was delivered. The ovarian fragmentation-in vitro activation approach is not only valuable for treating infertility of POI patients but could also be useful for middle-aged infertile women, cancer patients undergoing sterilizing treatments, and other conditions of diminished ovarian reserve.

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Section: Discussionmentioning

confidence: 96%

Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment

Kawamura

Cheng

Suzuki³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

723

685

View full text Add to dashboard Cite

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“…Muramatsu et al (2002) demonstrated that cysteine-rich protein 61, a secreted growth factor-inducible immediate early gene, is induced in proximal straight tubules of rodents within 2 hr of renal ischemia and can be detected in rat urine as early as 3-6 hr after renal injury. Cystatin C is a 13-kDa plasma protein that inhibits cysteine proteases and is freely filtered at the glomerulus.…”

Section: Discussionmentioning

confidence: 99%

Identification of Putative Gene Based Markers of Renal Toxicity

Amin¹,

Vickers²,

Sistare³

et al. 2004

Environ. Health Perspect.

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This study, designed and conducted as part of the International Life Sciences Institute working group on the Application of Genomics and Proteomics, examined the changes in the expression profile of genes associated with the administration of three different nephrotoxicants-cisplatin, gentamicin, and puromycin-to assess the usefulness of microarrays in the understanding of mechanism(s) of nephrotoxicity. Male Sprague-Dawley rats were treated with daily doses of puromycin (5-20 mg/kg/day for 21 days), gentamicin (2-240 mg/kg/day for 7 days), or a single dose of cisplatin (0.1-5 mg/kg). Groups of rats were sacrificed at various times after administration of these compounds for standard clinical chemistry, urine analysis, and histological evaluation of the kidney. RNA was extracted from the kidney for microarray analysis. Principal component analysis and gene expression-based clustering of compound effects confirmed sample separation based on dose, time, and degree of renal toxicity. In addition, analysis of the profile components revealed some novel changes in the expression of genes that appeared to be associated with injury in specific portions of the nephron and reflected the mechanism of action of these various nephrotoxicants. For example, although puromycin is thought to specifically promote injury of the podocytes in the glomerulus, the changes in gene expression after chronic exposure of this compound suggested a pattern similar to the known proximal tubular nephrotoxicants cisplatin and gentamicin; this prediction was confirmed histologically. We conclude that renal gene expression profiling coupled with analysis of classical end points affords promising opportunities to reveal potential new mechanistic markers of renal toxicity.

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“…Certain blood and urine markers of kidney injury such as serum creatinine, urea nitrogen as well as urine markers such as casts, fractional excretion of Na are insensitive and nonspecific for the diagnosis of acute kidney injury (32). Recently, urinary molecules have shown promise in both urine and animal studies including, neutrophil gelatinase associated lipocalcin (NGAL) (33,34), Kidney Injury Molecule-1 (Kim 1) (35,36), sodium/hydrogen exchanger isoform 3 (NHE3) (37), cytokines (38,39) cysteine rich protein 61 (40), actin (38), glutathione-Stransferases (41,42). These biomarkers have a great deal of promise in the ability to detect early kidney injury and aid with its subsequent management but need to be validated and confirmed in larger studies.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Detection of Promoter Hypermethylation as a Biomarker of Acute Kidney Injury During Transplantation

Mehta

Hoque

Ugarte

et al. 2006

Transplantation Proceedings

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Aberrant promoter hypermethylation, also known as epigenetics, is thought to be a promising biomarker approach to diagnose malignancies. Kidney repair after injury is a recapitulation of normal morphogenesis, with similarities to malignant transformation. We hypothesized that changes in urine epigenetics could be a biomarker approach during early kidney transplant injury and repair. We examined urine DNA for aberrant methylation of 2 gene promoters (DAPK CALCA) by quantitative methylation specific PCR from 13 deceased and 10 living donor kidney transplant recipients on postoperative day 2 and 65 healthy controls. Results were compared with clinical outcomes and to results of the kidney biopsy. Transplant recipients were significantly more likely to have aberrant hypermethylation of the CALCA gene promoter in urine than healthy controls (100% vs. 31%, p<0.0001). There was increased CALCA hypermethylation in the urine of deceased vs. living donor transplants (21.60 +/− 12.5 vs. 12.19 +/− 4.7 P=0.04). Furthermore, there was a trend towards increased aberrant hypermethylation of urine CALCA in patients with biopsy-proven acute tubular necrosis vs. acute rejection and slow or prompt graft function (mean: 20.40 +/− 6.9, 13.87 +/− 6.49, 17.17 +/− 13.4, P=0.67). However, there was no difference of CALCA hypermethylation in urine of patients with delayed graft function vs. those with slow or prompt graft function (16.9 +/− 6.2 vs. 18.5 +/− 13.7, respectively; P=0.5). There was no aberrant hypermethylation of DAPK in the urine of transplant patients. Urine epigenetics is a promising biomarker approach for acute ischemic injury in transplantation that merits future study.

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Early detection of cysteine rich protein 61 (CYR61, CCN1) in urine following renal ischemic reperfusion injury

Abstract: The secreted, cysteine-rich, heparin binding protein Cyr61 is rapidly induced in proximal straight tubules following renal ischemia, and excreted in the urine where it might serve as an early biomarker of renal injury.

Cited by 139 publications

References 40 publications

Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment

Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment

Identification of Putative Gene Based Markers of Renal Toxicity

Quantitative Detection of Promoter Hypermethylation as a Biomarker of Acute Kidney Injury During Transplantation

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