Urine survivin, E-cadherin and matrix metalloproteinases as novel biomarkers in children with chronic kidney disease

Musiał, Kinga; Bargenda, Agnieszka; Zwołińska, Danuta

doi:10.3109/1354750x.2015.1061598

Cited by 17 publications

(23 citation statements)

References 31 publications

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“…[ 30 , 50 ] Urinary TIMP-1, -2 excretions were reported to be increased in patients with CKD. [ 22 , 51 ] In our study, all patients showed elevated urinary TIMP-1, -2 excretions. In children with SRNS, urinary TIMP-1/Cr ratio was significantly higher than that in children with SDNS.…”

Section: Discussionsupporting

confidence: 59%

“…[ 21 ] Recent studies showed positive correlation between urinary TGF-beta excretion and urinary excretions of MMP-2 and -9 that confirm their profibrotic action. [ 22 ] Experimental data and human studies demonstrated that increased MMPs glomerular expression correlates positively with severity of glomerular damage and progression of kidney disease. [ 23 – 26 ] Recent studies in patients with chronic kidney disease (CKD), diabetic nephropathy, and after kidney transplantation demonstrated that higher serum levels and/or urinary excretions of MMPs and TIMPs might be biomarkers for an early stage of RF or its progression.…”

Section: Introductionmentioning

confidence: 99%

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Urinary metalloproteinases and tissue inhibitors of metalloproteinases as potential early biomarkers for renal fibrosis in children with nephrotic syndrome

Bieniaś¹,

Sikora²

2018

Medicine

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In chronic glomerulopathies, renal fibrosis (RF) results from extracellular matrix remodeling processes regulated by matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP). We assessed urinary (u-) and serum (s-) MMP-1, -2, -9, TIMP-1, -2 concentrations and MMP-1, -2, -9/TIMP-1, -2 ratios in children with nephrotic syndrome. Steroid-dependent and steroid-resistant nephrotic patients (SDNS-Ps and SRNS-Ps, respectively) were compared with respect to measured parameters. The correlations of measured parameters with magnitude of proteinuria and histopathological diagnosis were determined.The study comprised of 39 children with nephrotic syndrome and 20 healthy controls. Twenty-three patients had SDNS and 16 ones—SRNS. The concentrations MMPs and TIMPs were measured using enzyme-linked immunosorbent assay.In nephrotic patients, higher u-MMP-1, -2, -9/creatinine ratios and u-TIMP-1, -2/creatinine ratios were observed as compared with controls. Nephrotic children were also characterized by lower MMP-1, -2, -9/TIMP-1 ratios. In SRNS-Ps, u-MMP-2/creatinine ratio and u-TIMP-1/creatinine ratio were higher as compared with SDNS-Ps. Magnitude of proteinuria correlated positively with u-MMP-2/creatinine ratio and negatively with u-MMP-2/TIMP-1. In minimal change disease (MCD) patients as compared with those with other glomerulopathies, there was higher u-MMP-2/TIMP-1 ratio. No significant differences in s-MMPs, s-TIMPs, and s-MMPs/TIMPs ratios between nephrotic patients and controls were observed.Children with nephrotic syndrome are characterized by increased u-fibrotic biomarkers excretions. U-MMP-1, -2, -9 excretions and u-MMP-2/TIMP-1 ratio may become potential early biomarkers for RF. SRNS-Ps, those with heavier proteinuria and other than MCD glomerulopathies, seem to be more susceptible to early RF.

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Section: Discussionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Urinary metalloproteinases and tissue inhibitors of metalloproteinases as potential early biomarkers for renal fibrosis in children with nephrotic syndrome

Bieniaś¹,

Sikora²

2018

Medicine

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“…Adhesion signaling mediated by integrins were shown to induce EMT in association with TGF-b receptor signaling. MMP-2/9 play critical roles in tumor cell invasion and metastasis by hydrolyzing extracellular matrix [46]. In the present study, inhibition of metastasis is achieved as the OCT-modified daunorubicin plus dihydroartemisinin liposomes increase cell-cell adhesion by enhancing E-cadherin activity and markedly downregulate TGF-b1, VEGF, a5b1-integrin, and MMP-2/9 in breast cancer cells ( Figure 6).…”

Section: Discussionmentioning

confidence: 56%

Octreotide-modified liposomes containing daunorubicin and dihydroartemisinin for treatment of invasive breast cancer

Cheng

Peng

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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Tumor invasion is considered a major promoter in the initiation of tumor metastasis, which is supposed to cause most cancer-related deaths. In the present study, octreotide (OCT)-modified daunorubicin plus dihydroartemisinin liposomes were developed and characterized. Evaluations were undertaken on breast cancer MDA-MB-435S cells and MDA-MB-435S xenografts nude mice. The liposomes were ∼100 nm in size with a narrow polydispersity index. In vitro results showed that the OCT-modified daunorubicin plus dihydroartemisinin liposomes could enhance cytotoxicity and cellular uptake by OCT-SSTRs (somatostatin receptors)-mediated active targeting, block on tumor cell wound healing and migration by incorporating dihydroartemisinin. The action mechanism might be related to regulations on E-cadherin, α5β1-integrin, TGF-β1, VEGF and MMP2/9 in breast cancer cells. In vivo, the liposomes displayed a prolonged circulating time, more accumulation in tumor location, and a robust overall antitumor efficacy with no obvious toxicity at the test dose in MDA-MB-435S xenograft mice. In conclusion, the OCT-modified daunorubicin plus dihydroartemisinin liposomes could prevent breast cancer invasion, hence providing a possible strategy for treatment of metastatic breast cancer.

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“…They have even warned about targeting this molecule in cancer therapy because of its harmful effects on tubular integrity [ 17 ]. Musiał et al studying chronic kidney disease (CKD) in children have observed increased amounts of survivin in patients' urine samples which was not in concordance with its serum level, so they suggested that this molecule is expressed in renal tissue probably as a protective factor against progressive damage and recommended survivin as a diagnostic maker in CKD follow-up; however, it could be presumed that survivin has been released and shed from tubules into the urine flow because of tissue destruction as a consequence of CKD pathogenesis [ 18 ].…”

Section: Survivin In Transplantationmentioning

confidence: 99%

Antiapoptotic Molecule Survivin in Transplantation: Helpful or Harmful?

Assadiasl

Mousavi

Amirzargar

2018

Journal of Transplantation

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Survivin, an antiapoptotic molecule from inhibitor of apoptosis protein (IAP) family, is most known for its implication in cancer as there are some efforts to apply it for diagnostic as well as therapeutic purposes in oncology. On the other hand, it could be a useful molecule to be positively targeted when trying to save tissue and promote cells viability. Since protecting the allograft from ischemia reperfusion injury and inflammation-induced damage is a considerable objective in transplantation, it is reasonable to take advantage from antiapoptotic agents like survivin in order to achieve this goal. However, survivin's potential ability to induce malignancies makes some concerns about its use in clinic. The other barrier is this molecule's involvement in lymphocytes development and proliferation which might increase the risk of graft rejection due to adaptive immune system overactivation. In this review we summarize the few studies carried out about survivin's effect on graft survival and probable advantages and disadvantages of its overexpression in transplantation.

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Urine survivin, E-cadherin and matrix metalloproteinases as novel biomarkers in children with chronic kidney disease

Abstract: The observed parameter changes indicate apoptosis, tissue remodeling and fibrosis in CKD children. Urine survivin may become a new biomarker of kidney-specific EMT.

Cited by 17 publications

References 31 publications

Urinary metalloproteinases and tissue inhibitors of metalloproteinases as potential early biomarkers for renal fibrosis in children with nephrotic syndrome

Urinary metalloproteinases and tissue inhibitors of metalloproteinases as potential early biomarkers for renal fibrosis in children with nephrotic syndrome

Octreotide-modified liposomes containing daunorubicin and dihydroartemisinin for treatment of invasive breast cancer

Antiapoptotic Molecule Survivin in Transplantation: Helpful or Harmful?

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