Elevation of Serum Levels of Metalloproteinase-1, Tissue Inhibitor of Metalloproteinase-1 and Type IV Collagen, and Plasma Levels of Metalloproteinase-9 in Polycystic Kidney Disease

Nakamura, Tsukasa; Ushiyama, Chifuyu; Suzuki, Shingo; Ebihara, Isao; Shimada, Noriaki; Koide, Hikaru

doi:10.1159/000013552

Cited by 68 publications

(41 citation statements)

References 19 publications

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“…Differences of MMP activities between patients and healthy control subjects were not a consequence of the difference in kidney function per se, because our patients with glomerulonephritis experienced only mild renal failure and because subjects with comparable noninflammatory kidney failure as a result of ADPKD displayed similar results as the healthy control group. In this respect, the slightly higher levels MMP-1 and of MMP-9 were in line with a previous investigation of a somewhat older group of predominantly female patients with ADPKD (37). Moreover, our patients with glomerulonephritis excreted significantly higher amounts of both MMP-2 and MMP-9 in their urine than healthy control subjects, possibly reflecting ongoing glomerular inflammation.…”

Section: Discussionsupporting

confidence: 92%

Angiotensin-Converting Enzyme Inhibition but not Angiotensin II Receptor Blockade Regulates Matrix Metalloproteinase Activity in Patients with Glomerulonephritis

Lods

Ferrari

Frey

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Equivalent long-term effects on the kidney are attributed to angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB). Nevertheless, it is unknown to which degree effects of these compounds on individual inflammatory mediators, including matrix metalloproteinases (MMP), are comparable. On the basis of structural and functional differences, it was hypothesized that ACEI and ARB differentially regulate MMP activity. In a randomized, prospective crossover trial, the effect of an ACEI (fosinopril; 20 mg/d) and of an ARB (irbesartan; 150 mg/d) on MMP activity was evaluated. Ten hypertensive patients with glomerulonephritis and normal or mildly reduced creatinine clearance were studied. MMP activity and tissue inhibitors of metalloproteinase (TIMP) levels were analyzed in serum and urine: without therapy, with ACEI, with ARB, and with both agents combined. Treatment periods continued for 6 wk separated by periods of 4 wk each without therapy. Untreated patients with glomerulonephritis displayed distinctively higher serum levels of MMP-2 but much lower MMP-1/-8/-9 concentrations compared with healthy control subjects. Immunohistology of MMP-2 and MMP-9 in kidney biopsy specimen was accordingly. However, these patients excreted higher amounts of MMP-2 and MMP-9 in urine than healthy control subjects, possibly reflecting ongoing glomerular inflammation. In patients with glomerulonephritis, ACEI significantly reduced overall MMP serum activity to 25%, whereas ARB did not show any effect. Activities of MMP-1/-2/-8/-9 were also significantly inhibited by fosinopril but not by irbesartan. Levels of TIMP-1/-2 remained unaffected. In conclusion, ACEI and ARB differentially regulate MMP activity, which may ultimately have consequences in certain types of MMP-dependent glomerulonephritis.Glomerular inflammatory diseases represent frequent and often difficult-to-treat causes of end-stage kidney failure. Hypertension and proteinuria are important independent determinants and risk factors for progression of these diseases (1). Therefore, these two conditions are prime targets for the therapy of all types of glomerulonephritis.Pharmacologic inhibition of the renin-angiotensin system by angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) has been particularly well demonstrated to treat high BP and proteinuria successfully (1). Moreover, the decline of kidney function occurring in diabetic as well as in nondiabetic glomerulopathies was greatly reduced by these agents in many investigations (2,3). Although ARB have only recently been introduced to common clinical use, several studies reported equivalent renoprotection for both classes of agents, ACEI and ARB (1). However, the issue of long-term effects with regard to the kidney is not yet fully resolved, and the identification of patient groups in which one of these agents demonstrates potential advances over the other one remains of pivotal clinical interest.Angiotensin II plays a key role...

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Section: Discussionsupporting

confidence: 92%

Angiotensin-Converting Enzyme Inhibition but not Angiotensin II Receptor Blockade Regulates Matrix Metalloproteinase Activity in Patients with Glomerulonephritis

Lods

Ferrari

Frey

et al. 2003

Journal of the American Society of Nephrology

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“…chronic inflammatory processes and malignancy) (21). In fact, elevated serum levels of MMPs have been reported in polycystic kidney disease (22), multiple sclerosis (23), rheumatoid arthritis (24), and many different human tumours including carcinomas of the lung, colon, breast and prostate (25)(26)(27)(28).…”

mentioning

confidence: 99%

Increased release and activity of matrix metalloproteinase‐9 in patients with mandibuloacral dysplasia type A, a rare premature ageing syndrome

Lombardi

Fasciglione

D’Apice³

et al. 2008

Clinical Genetics

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Sbraccia P, Marini S, Borgiani P, Coletta M, Novelli G. Increased release and activity of matrix metalloproteinase-9 in patients with mandibuloacral dysplasia type A, a rare premature ageing syndrome.Mandibuloacral dysplasia type A (MADA; OMIM 248370), a rare disorder caused by mutation in the LMNA gene, is characterized by post-natal growth retardation, craniofacial and skeletal anomalies (mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of cranial sutures, low bone mass and joint contractures), cutaneous changes and partial lipodystrophy. Little is known about the molecular mechanisms by which LMNA mutations produce bone alterations. An altered bone extracellular matrix (ECM) remodelling could play a pivotal role in this disorder and influence part of the typical bone phenotype observed in patients. Therefore, we have focused our investigation on matrix metalloproteinases (MMPs), which are degradative enzymes involved in ECM degradation and ECM remodelling, thus likely contributing to the altered bone mineral density and bone metabolism values seen in five MADA patients. We evaluated the serum levels of several MMPs involved in bone development, remodelling and homeostasis, such as MMP-9, -2, -3, -8 and -13, and found that only the 82 kDa active enzyme forms of MMP-9 are significantly higher in MADA sera compared with healthy controls (n ¼ 16). The serum level of MMP-3 was instead lower in all patients. No significant differences were observed between controls and MADA patients for the serum levels of MMP-2, -8 and -13 and of tissue inhibitor of metalloproteinase 2, a natural inhibitor of MMP-9. Similarly, normal serum levels of tumour necrosis factor alpha (TNF-a), interleukin (IL)-6 and IL-1b were detected. These data suggest a possible involvement of MMP-9 in MADA disease, underlying the potential use in diagnosis and therapy.

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“…Elevated serum levels of MMPs have been reported in, for example, polycystic kidney disease (19), systemic sclerosis (20), rheumatoid arthritis (21), and cancer. In some diseases, such as acute viral hepatitis, however, serum levels of MMPs are reduced (22).…”

mentioning

confidence: 99%

High Serum Levels of Matrix Metalloproteinase-9 and Matrix Metalloproteinase-1 Are Associated with Rapid Progression in Patients with Metastatic Melanoma

Nikkola

Vihinen

Vuoristo

et al. 2005

Clinical Cancer Research

166

127

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Purpose: Matrix metalloproteinases (MMP) are proteolytic enzymes that play an important role in various aspects of cancer progression. In the present work, we have studied the prognostic significance of serum levels of gelatinase B (MMP-9), collagenase-1 (MMP-1), and collagenase-3 (MMP-13) in patients with advanced melanoma. Experimental Design: Total pretreatment serum levels of MMP-9 in 71patients and MMP-1and MMP-13 in 48 patients were determined by an assay system based on ELISA. Total MMP levels were also assessed in eight healthy controls. The active and latent forms of MMPs were defined by usingWestern blot analysis and gelatin zymography. Results: Patients with high serum levels of MMP-9 (z376.6 ng/mL; n = 19) had significantly poorer overall survival (OS) than patients with lower serum MMP-9 levels (n = 52; median OS, 29.1 versus 45.2 months; P = 0.033). High MMP-9 levels were also associated with visceral or bone metastasis (P = 0.027), elevated serum alkaline phosphatase level (P = 0.0009), and presence of liver metastases (P = 0.032). Serum levels of MMP-1and MMP-13 did not correlate with OS. MMP-1 and MMP-9 were found mainly in latent forms in serum, whereas the majority of MMP-13 in serum was active (48 kDa) form. MMP-13 was found more often in active form in patients (mean, 99% of the total MMP-13 level) than in controls (mean, 84% of the total MMP-13 level; P < 0.0001). After initiating the therapy, patients with elevated levels of MMP-1 (z29.8 ng/mL, n = 10) progressed more rapidly than patients with lower levels (median, 1.9 versus 3.5 months; P = 0.023). Serum levels of MMP-9 and MMP-13 did not correlate with the time to progression (TTP). In multivariate analysis with age and gender, MMP-9 or MMP-1turned out to be independent prognostic factors for OS [P = 0.039; hazard ratio (HR), 1.8; 95% confidence interval (95% CI), 1.03-3.3] or TTP (P = 0.023; HR, 2.7; 95% CI, 1.15-6.4), respectively. Conclusions: Our findings provide evidence that MMP-1, MMP-9, and MMP-13 play important roles at different phases of metastatic melanoma spread and that serum MMP-9, in particular, could have clinical value in identifying patients at high risk for melanoma progression.

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Elevation of Serum Levels of Metalloproteinase-1, Tissue Inhibitor of Metalloproteinase-1 and Type IV Collagen, and Plasma Levels of Metalloproteinase-9 in Polycystic Kidney Disease

Cited by 68 publications

References 19 publications

Angiotensin-Converting Enzyme Inhibition but not Angiotensin II Receptor Blockade Regulates Matrix Metalloproteinase Activity in Patients with Glomerulonephritis

Angiotensin-Converting Enzyme Inhibition but not Angiotensin II Receptor Blockade Regulates Matrix Metalloproteinase Activity in Patients with Glomerulonephritis

Increased release and activity of matrix metalloproteinase‐9 in patients with mandibuloacral dysplasia type A, a rare premature ageing syndrome

High Serum Levels of Matrix Metalloproteinase-9 and Matrix Metalloproteinase-1 Are Associated with Rapid Progression in Patients with Metastatic Melanoma

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