Differential regulation of glomerular gelatinase B (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in obese Zucker rats

Schaefer, Liliana; Han, Xiao; August, Christian; Matzkies, F; Lorenz, Tierney K.; Schaefer, Roland M.

doi:10.1007/s001250050785

Cited by 36 publications

(27 citation statements)

References 40 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although not reaching statistical significance, pair-feeding also reduced expression of fibronectin (expressed in states of mesangial expansion, such as early in glomerulosclerosis) and the 92-kDa collagenase (e.g., MMP-9, Gelatinase B, up-regulated in developing glomerular disease, when collagen IV is being actively synthesized and turned over). Each of these has been implicated in glomerular disease associated with hyperlipidemia in rat models (13)(14)(15)(16). Statistical significance was not reached in the latter two genes, primarily due to the relatively heterogeneous gene expression observed in AL obese rats in this and other reports (6,17).…”

Section: Glomerular Gene Expressionmentioning

confidence: 58%

Hyperphagia as a Mediator of Renal Disease Initiation in Obese Zucker Rats

et al. 2001

View full text Add to dashboard Cite

Objective: We sought to determine whether prevention of overeating would block the very earliest manifestations of renal injury in young obese Zucker rats (OZRs). Research Methods and Procedures: Three groups of rats were studied, obese (fa/fa) Zucker rats and lean (Fa/Fa). Zucker controls were allowed to feed ad libitum, whereas a group of obese (fa/fa) Zucker rats was pair-fed to the lean group. Urine albumin and serum lipids were studied weekly from 6 to 10 weeks of age. Renal pathology and renal glomerular gene expression were examined when the rats were killed at 10 weeks of age. Results: Obese rats fed ad libitum developed significant albuminuria by 6 weeks of age, increasing at each subsequent time-point. This increase was completely blocked by pair-feeding. Serum triglycerides were significantly increased in obese rats fed ad libitum vs. the other groups. Urine albumin correlated significantly with both body weight and serum triglyceride level. Renal histopathology was normal in all groups. Analysis of gene expression of glomerular proteins by reverse transcriptase-polymerase chain reaction revealed that pair-feeding attenuated the increased expression of glomerular desmin, fibronectin, and the 92-kDa collagenase that was seen in obese animals fed ad libitum. Discussion: Prevention of overeating in young OZR normalizes albuminuria and attenuates the pathogenic alterations in glomerular gene expression seen at the initiation of renal disease in obese animals allowed to feed ad libitum. This model may be relevant for studying the early endorgan effects of obesity.

show abstract

Section: Glomerular Gene Expressionmentioning

confidence: 58%

Hyperphagia as a Mediator of Renal Disease Initiation in Obese Zucker Rats

et al. 2001

View full text Add to dashboard Cite

show abstract

“…Marked decreases in MMP-9 mRNA expression and enzymatic activity were also noted in the glomeruli of diabetic obese Zucker rats (31). We observed that baseline MMP-9 expression and activity were markedly decreased in MC after long-term exposure to high ambient glucose levels (32,33).…”

mentioning

confidence: 53%

Association of a Decreased Number of d(CA) Repeats in the Matrix Metalloproteinase-9 Promoter with Glomerulosclerosis Susceptibility in Mice

Fornoni

Wang

Lenz

et al. 2002

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Abstract. The genetic background plays an important role in the development of progressive glomerulosclerosis. However, no marker is available for the reliable prediction of genetic susceptibility to glomerulosclerosis. Because matrix metalloproteinase-9 (MMP-9) levels are decreased in models of glomerulosclerosis and MMP-9 promoter polymorphism has been observed among patients with diabetic nephropathy, MMP-9 could be one such marker. The object of this study was to determine whether MMP-9 promoter polymorphism was associated with altered MMP-9 expression in mesangial cells (MC) from two mouse strains, i.e., ROP (glomerulosclerosis prone) and B6SJL (glomerulosclerosis resistant). ROP MC expressed 12-fold less MMP-9 mRNA. The MMP-9 promoter in ROP MC contained fewer d(CA) repeats, which was associated with lower MMP-9 expression and activity. Phorbol-12-myristate-13-acetate (3 to 60 ng/ml) increased MMP-9 expression in both MC types (3-to 4.5-fold), but the level in ROP MC never reached that in B6SLJ MC. Although reciprocal transfection of ROP and B6SJL MMP-9 promoter constructs into B6SJL and ROP cells revealed that the promoters were functional in both cell types, the B6SJL promoter was less responsive to phorbol-12-myristate-13-acetate stimulation when transfected into ROP MC, suggesting a role for other factors. In conclusion, the MMP-9 promoter exhibits a decreased number of d(CA) repeats in the sclerosis-prone strain. Because fewer d(CA) repeats associated with decreased MMP-9 expression in MC, it might be a genetic marker for glomerulosclerosis.

show abstract

“…MMP-2 is predominantly inhibited by TIMP-2 17 and TIMP-4, 18 while MMP-9 is inhibited mainly by TIMP-1. 19 An imbalance between MMPs and TIMPs expression was shown in recent studies to be connected with a variety of different tumours, for example, lung, 20 colon, 21 breast 22 and prostate. 23 In the present study, the expression of MMP-2 and -9, and TIMP-1 and -2 in prostate cancer tissue was examined using immunohistochemical methods.…”

Section: Introductionmentioning

confidence: 99%

Expression of matrix metalloproteinases (MMP-2 and -9) and their inhibitors (TIMP-1 and -2) in prostate cancer tissue

Brehmer

Biesterfeld²,

Jakse

2003

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

Matrix metalloproteinases (MMPs) have been implicated in progression and metastases of different tumours. The balance between the MMPs and their natural inhibitors (tissue inhibitors of matrix metalloproteinases; TIMP) seems to be an important factor related to this role. Here, the expression of MMP-2 and -9 along with TIMP-1 and -2 was examined in prostate cancer tissue. A total of 40 radical prostatectomy specimens were embedded in paraffin and immunohistochemical staining was performed to detect MMP-2 and -9, and TIMP-1 and -2. The immunoreactivity was assessed semiquantitively using routine light microscopy. The intensity of staining was correlated to preoperative PSA, T category, Gleason score and clinical parameters of the specimens. The imbalance of MMPs and TIMPs was recognised as a significant loss of TIMP-1 in malignant epithelium and an upregulation of MMPs. Palpable tumours (T2, T3) expressed significantly more MMP-2 and significantly less MMP-9 than T1c tumours. Our data are in accordance with other literature reports in that an imbalance of MMPs and TIMPs is found in malignant tumours. The observed imbalance of MMP and TIMP is mainly caused by a loss of TIMP-1. Furthermore, palpable tumours demonstrated significantly more MMP-2 and significantly less MMP-9 expression than nonpalpable tumours.

show abstract

Differential regulation of glomerular gelatinase B (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in obese Zucker rats

Cited by 36 publications

References 40 publications

Hyperphagia as a Mediator of Renal Disease Initiation in Obese Zucker Rats

Hyperphagia as a Mediator of Renal Disease Initiation in Obese Zucker Rats

Association of a Decreased Number of d(CA) Repeats in the Matrix Metalloproteinase-9 Promoter with Glomerulosclerosis Susceptibility in Mice

Expression of matrix metalloproteinases (MMP-2 and -9) and their inhibitors (TIMP-1 and -2) in prostate cancer tissue

Contact Info

Product

Resources

About