RRC ID |
11827
|
著者 |
Hayashi K, Sasamura H, Ishiguro K, Sakamaki Y, Azegami T, Itoh H.
|
タイトル |
Regression of glomerulosclerosis in response to transient treatment with angiotensin II blockers is attenuated by blockade of matrix metalloproteinase-2.
|
ジャーナル |
Kidney Int
|
Abstract |
Understanding mechanisms that contribute to the regression of glomerulosclerosis is important for developing new strategies to treat chronic kidney disease. We reported that transient high-dose treatment with an angiotensin receptor blocker causes regression of renal arteriolar hypertrophy and hypertension in spontaneously hypertensive rats. To extend those findings to another form of kidney disease, we examined the short- and long-term effects of transient high-dose angiotensin receptor blocker treatment in a mouse model of adriamycin-induced glomerulosclerosis. A 2-week course of candesartan caused a dose-dependent regression of established glomerulosclerotic lesions sustained for over 6 months following cessation of treatment. Highly sensitive in situ zymography and activity assays showed that glomerular matrix metalloproteinase (MMP)-2 activity was increased after high-dose angiotensin blocker therapy. Treatment of cultured podocytes with candesartan resulted in an increase in MMP-2 activity. The regression of glomerulosclerosis was partially attenuated in mice pretreated with the MMP inhibitor doxycycline, as well as in MMP-2 knockout mice. Our results suggest that transient high-dose angiotensin receptor blocker treatment effectively induced sustained regression of glomerulosclerosis by a mechanism mediated, in part, by changes in MMP-2 activity.
|
巻・号 |
78(1)
|
ページ |
69-78
|
公開日 |
2010-7-1
|
DOI |
10.1038/ki.2010.81
|
PII |
S0085-2538(15)54398-6
|
PMID |
20375993
|
MeSH |
Angiotensin II / pharmacology
Angiotensin II / therapeutic use
Angiotensin Receptor Antagonists*
Angiotensins / pharmacology
Angiotensins / therapeutic use
Animals
Antihypertensive Agents / pharmacology
Antihypertensive Agents / therapeutic use
Benzimidazoles
Biphenyl Compounds
Hypertension / drug therapy
Hypertension / pathology
Hypertension / physiopathology
Kidney / drug effects
Kidney / pathology
Kidney / physiopathology
Kidney Diseases / drug therapy*
Kidney Diseases / pathology
Kidney Diseases / physiopathology*
Kidney Glomerulus / drug effects
Kidney Glomerulus / pathology
Kidney Glomerulus / physiopathology
Matrix Metalloproteinase 2 / pharmacology
Matrix Metalloproteinase Inhibitors*
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
Mice, Knockout
Random Allocation
Rats
Rats, Inbred SHR
Receptors, Angiotensin / therapeutic use
Tetrazoles
Time Factors
|
IF |
8.945
|
引用数 |
31
|
WOS 分野
|
UROLOGY & NEPHROLOGY
|
リソース情報 |
実験動物マウス |
RBRC00398 |