التفاصيل البيبلوغرافية
| العنوان: |
Matrix metalloproteinase-9 deficiency attenuates diabetic nephropathy by modulation of podocyte functions and dedifferentiation |
| المؤلفون: |
Li, Szu-Yuan, Huang, Po-Hsun, Yang, An-Hang, Tarng, Der-Cherng, Yang, Wu-Chang, Lin, Chih-Ching, Chen, Jaw-Wen, Schmid-Schönbein, Geert, Lin, Shing-Jong |
| المصدر: |
Kidney International, vol 86, iss 2 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2014 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Kidney Disease, Diabetes, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Renal and urogenital, Albuminuria, Animals, Cell Dedifferentiation, Cells, Cultured, Cytokines, Diabetes Mellitus, Experimental, Diabetic Nephropathies, Humans, Male, Matrix Metalloproteinase 9, Mice, Knockout, Podocytes, Up-Regulation, diabetic nephropathy, matrix metalloproteinases, podocyte, Clinical Sciences, Urology & Nephrology |
| جغرافية الموضوع: |
358 - 369 |
| الوصف: |
Diabetic nephropathy is characterized by excessive deposition of extracellular matrix protein and disruption of the glomerular filtration barrier. Matrix metalloproteinases (MMPs) affect the breakdown and turnover of extracellular matrix protein, suggesting that altered expression of MMPs may contribute to diabetic nephropathy. Here we used an MMP-9 gene knockout mouse model, with in vitro experiments and clinical samples, to determine the possible role of MMP-9 in diabetic nephropathy. After 6 months of streptozotocin-induced diabetes, mice developed markedly increased albuminuria, glomerular and kidney hypertrophy, and thickening of the glomerular basement membrane. Gelatin zymographic analysis and western blotting showed that there was enhanced MMP-9 protein production and activity in the glomeruli. However, MMP-9 knockout in diabetic mice significantly attenuated these nephropathy changes. In cultured podocytes, various cytokines related to diabetic nephropathy including TGF-β1, TNF-α, and VEGF stimulated MMP-9 secretion. Overexpression of endogenous MMP-9 induced podocyte dedifferentiation. MMP-9 also interrupted podocyte cell integrity, promoted podocyte monolayer permeability to albumin, and extracellular matrix protein synthesis. In diabetic patients, the upregulation of urinary MMP-9 concentrations occurred earlier than the onset of microalbuminuria. Thus, MMP-9 seems to play a role in the development of diabetic nephropathy. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt2kg7d1hg; https://escholarship.org/uc/item/2kg7d1hgTest |
| الإتاحة: |
https://escholarship.org/uc/item/2kg7d1hgTest |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.85408B2F |
| قاعدة البيانات: |
BASE |
