Levels of urinary matrix metalloproteinase‐9 (MMP‐9) and renal injuries in patients with type 2 diabetic nephropathy

Tashiro, Kensuke; Koyanagi, Ichiro; Ohara, Ikko; Ito, Takamichi; Saitoh, Akemi; Horikoshi, Satoshi; Tomino, Yasuhiko

doi:10.1002/jcla.20024

Cited by 60 publications

(52 citation statements)

References 13 publications

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“…The MMP-9 expression level in the clinical DN group was higher than in the early DN group. This was consistent with the conclusions on the research on DN carried out by Tashiro K et al [11], in which the levels of MMP-9 in many albuminuria diabetic patients were significantly higher than that in the normal control group, and this increasing degree was consistent with the clinical staging of the disease. In DN patients, the expression of MMP-9 protein and its catalytic activity increased.…”

Section: Discussionsupporting

confidence: 80%

Badanie zależności między metylacją regionu promotora genu MMP-9 a nefropatią cukrzycową

Yang¹,

Feng²,

Yu³

et al. 2018

Endokrynologia Polska

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Introduction: This study aims to explore the relationship between the methylation of matrix metalloproteinase (MMP)-9 gene promoter region and diabetic nephropathy (DN) through the detection of the methylation level of MMP-9 gene promoter region in the peripheral blood of patients with DN in different periods and serum MMP-9 concentration. Material and methods: The methylation level of the MMP-9 gene promoter region was detected by methylation-specific polymerase chain reaction (MSP), and the content of MMP-9 in serum was determined by enzyme-linked immunosorbent assay (ELISA). Results: Results of the statistical analysis revealed that serum MMP-9 protein expression levels gradually increased in patients in the simple diabetic group, early diabetic nephropathy group, and clinical diabetic nephropathy group, compared with the control group, and the difference was statistically significant (P < 0.05). Compared with the control group, the methylation levels of MMP-9 gene promoter regions gradually decreased in patients in the simple diabetic group, early diabetic nephropathy group, and clinical diabetic nephropathy group, and the difference was statistically significant (P < 0.05). Furthermore, correlation analysis results indicated that the demethylation levels of the MMP-9 gene promoter region were positively correlated with serum protein levels, urinary albumin-to-creatinine ratio (UACR), urea, and creatinine, and was negatively correlated with GFR. Conclusions:The demethylation of the MMP-9 gene promoter region may be involved in the occurrence and development of diabetic nephropathy by regulating the expression of MMP-9 protein in serum. (Endokrynol Pol 2018; 69 (3): 269-275)

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Section: Discussionsupporting

confidence: 80%

Badanie zależności między metylacją regionu promotora genu MMP-9 a nefropatią cukrzycową

Yang¹,

Feng²,

Yu³

et al. 2018

Endokrynologia Polska

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“…Whether the increased proteolytic cleavage of ENaC contributes to renal Na + retention in nephrotic syndrome warrants future analysis. The concentration of proteases may also be increased in the urine of diabetic patients [321] which is supported by a recent report that plasmin is increased in the urine of obese, diabetic and hypertensive ZSF1 rats [248]. Thus, it is tempting to speculate that an inappropriate ENaC activation by elevated levels of urinary proteases may contribute to arterial hypertension associated with diabetes mellitus and metabolic syndrome.…”

Section: Regulation Of Enac By Proteasesmentioning

confidence: 48%

Regulated sodium transport in the renal connecting tubule (CNT) via the epithelial sodium channel (ENaC)

Loffing

Korbmacher

2009

Pflugers Arch - Eur J Physiol

145

139

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The aldosterone-sensitive distal nephron (ASDN) includes the late distal convoluted tubule 2, the connecting tubule (CNT) and the collecting duct. The appropriate regulation of sodium (Na + ) absorption in the ASDN is essential to precisely match urinary Na + excretion to dietary Na + intake whilst taking extra-renal Na + losses into account. There is increasing evidence that Na + transport in the CNT is of particular importance for the maintenance of body Na + balance and for the long-term control of extracellular fluid volume and arterial blood pressure. Na + transport in the CNT critically depends on the activity and abundance of the amiloride-sensitive epithelial sodium channel (ENaC) in the luminal membrane of the CNT cells. As a rate-limiting step for transepithelial Na + transport, ENaC is the main target of hormones (e.g. aldosterone, angiotensin II, vasopressin and insulin/insulinlike growth factor 1) to adjust transepithelial Na + transport in this tubular segment. In this review, we highlight the structural and functional properties of the CNT that contribute to the high Na + transport capacity of this segment. Moreover, we discuss some aspects of the complex pathways and molecular mechanisms involved in ENaC regulation by hormones, kinases, proteases and associated proteins that control its function. Whilst cultured cells and heterologous expression systems have greatly advanced our knowledge about some of these regulatory mechanisms, future studies will have to determine the relative importance of the various pathways in the native tubule and in particular in the CNT.

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“…Importantly, increased MMP-9 in the plasma precedes the development of microalbuminuria in patients without changes in either MMP-1 or TIMP-1 levels (27). This finding is supported by more recent data demonstrating that urinary levels of MMP-9 are elevated in type 2 diabetic patients, and correlated with albuminuria (83). In human diabetic patients, expression of MMP-24 correlated with tubular atrophy (68).…”

Section: Diabetic Nephropathymentioning

confidence: 64%

Role of matrix metalloproteinases in renal pathophysiologies

Catania¹,

Chen²,

Parrish³

2007

American Journal of Physiology-Renal Physiology

338

305

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Matrix metalloproteinases (MMPs) are a large family of proteinases that remodel extracellular matrix (ECM) components and cleave a number of cell surface proteins. MMP activity is regulated via a number of mechanisms, including inhibition by tissue inhibitors of metalloproteinases (TIMPs). Originally thought to cleave only ECM proteins, MMP substrates are now known to include signaling molecules (growth factor receptors) and cell adhesion molecules. Recent data suggest a role for MMPs in a number of renal pathophysiologies, both acute and chronic. This review will focus on the expression and localization of MMPs and TIMPs in the kidney, as well as summarizing the current information linking these proteins to acute kidney injury, glomerulosclerosis/tubulointerstitial fibrosis, chronic allograft nephropathy, diabetic nephropathy, polycystic kidney disease, and renal cell carcinoma.acute kidney injury; chronic allograft nephropathy; diabetic nephropathy; glomerulosclerosis; MMP; polycystic kidney disease; tissue inhibitor of metalloproteinase; tubulointerstitial fibrosis; renal cell carcinoma MATRIX METALLOPROTEINASES (MMPs) are zinc-containing endopeptidases that are involved in remodeling the extracellular matrix (ECM) and are crucial for tissue development and homeostasis. All MMPs are multidomain enzymes, generally consisting of a prodomain, a catalytic domain, a hinge region, and a hemopexin-like domain. Most MMPs are secreted as proMMPs; activation usually requires cleavage of the prodomain by plasmin or other MMPs (88). The propeptide sequence contains a conserved cysteine switch (PRCGXPD) to stabilize and inhibit the catalytic zinc ion, which is bound in a conserved HEXGHXXGXXH motif (53). The hemopexin-like domain is characterized by a "propeller" of four twisted ␤-sheets, which are thought to confer substrate recognition (53). Together, the hinge region and the hemopexin-like domain unravel substrate proteins for subsequent degradation. Originally thought to cleave only ECM proteins, this family of enzymes is now known to cleave a number of non-ECM substrates as well. For example, cell adhesion molecules (cadherins and integrins) and both growth factors and their receptors (TGF-␤, FGF-R1) are targeted by MMPs (74).Tissue inhibitors of metalloproteinases (TIMPs) are endogenous, specific inhibitors that bind and inhibit MMPs. Four TIMPs (TIMP-1-4) have been identified in vertebrates; these proteins share a similar structure which fits into the active site of the MMP catalytic domain. TIMPs inhibit all MMPs, except TIMP-1, which does not inhibit . A number of other MMP inhibitors have been identified, including RECK (81), ␣2-macroglobulin (4), and tissue factor pathway inhibitor-2 (33).MMPs are classified into six groups based on substrate and sequence homology: collagenases, gelatinases, stromelysins, matrilysins, membrane-type matrix metalloproteinases and "other MMPs" (Fig. 1). Collagenases [MMP-1, -8 (neutrophil collagenase), -13, and -18 (Xenopus laevis collagenase)] cleave collagens I, II, and III at a...

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Levels of urinary matrix metalloproteinase‐9 (MMP‐9) and renal injuries in patients with type 2 diabetic nephropathy

Cited by 60 publications

References 13 publications

Badanie zależności między metylacją regionu promotora genu MMP-9 a nefropatią cukrzycową

Badanie zależności między metylacją regionu promotora genu MMP-9 a nefropatią cukrzycową

Regulated sodium transport in the renal connecting tubule (CNT) via the epithelial sodium channel (ENaC)

Role of matrix metalloproteinases in renal pathophysiologies

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