TITLE

Effects of Losartan on Urinary Secretion of Extracellular Matrix and Their Modulators in Type 2 Diabetes Mellitus Patients with Microalbuminuria

AUTHOR(S)
Woo, Vincent; Lian-Song ni; Hak, Dixie; Bernard, Lori; Fuqin Zhu; Khan, Shagufta; Ma, Gouping M.; Penner, Brian; Shen, Garry X.
PUB. DATE
December 2006
SOURCE
Clinical & Investigative Medicine;Dec2006, Vol. 29 Issue 6, p365
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Purpose: Angiotensin II receptor Type 1 antagonists postpone the development of nephropathy in type 2 diabetes mellitus (DM). We hypothesize that Losartan may ameliorate renal function in diabetic patients through the regulation on the generation of transforming growth factor (TGF)-β and fibrinolytic regulators. Methods: Twenty-two type 2 DM patients with microalbuminuria were treated with 50–100 mg/day of Losartan for 6 months. Urinary secretion of TTGF-, plasminogen activator inhibitor-1 (PAI-1), tissue and urokinase plasminogen activators (tPA and uPA) fibronectin, collagen IV and plasma levels of TGF-β, PAI-1, tPA and uPA of the patients before and after the treatment were analyzed using enzyme-linked immunoabosorbance assay. Results: Losartan effectively reduced arterial blood pressure and urinary albumin excretion. The levels of TGF-β in urine, but no in plasma, were reduced after 2, 4 and 6 months of the treatment (-32% to -48%, P<0.05 or 0.01). Urinary or plasma levels of PAI-1, tPA or uPA, and urinary secretion of fibronectin or collagen IV were not significantly altered Losartan treatment. Urinary levels of collagen IV positively correlated with uPA, and that of fibronectin negatively correlated with PAI-1 in the patients (P<0.01). Urinary TGF-β negatively correlated uPA in urine of the patients (<0.01). Conclusion: Losartan reduced excretion of TGF-β and albumin in type 2 DM patients with microalbuminuria. Fibrinolytic regulators and TGF-β are implicated in the regulation of ECM turnover in kidneys of the patients with diabetic nephropathy.
ACCESSION #
23637430

 

Related Articles

  • High glucose down-regulates angiotensin II binding via the PKC-MAPK-cPLA2 signal cascade in renal proximal tubule cells. Park, Soo Hyun; Woo, Chang Hoon; Kim, Jae Hong; Lee, Jang Hern; Yang, Il Suk; Park, Kwon Moo; Han, Ho Jae // Kidney International;Mar2002, Vol. 61 Issue 3, p913 

    Background: It has been reported that renal renin-angiotensin system contributes to the development of diabetic nephropathy. However, the mechanism of angiotensin II receptor regulation in diabetic condition has not been elucidated.Methods: The effects of high glucose...

  • Plasminogen activator inhibitor-1 deficiency retards diabetic nephropathy. Nicholas, Susanne B.; Aguiniga, Elsa; Ren, Yuelan; Kim, Jason; Wong, Joyce; Govindarajan, Nalini; Noda, Masakuni; Wang, Wei; Kawano, Yasuko; Collins, Alan; Hsueh, Willa A. // Kidney International;Apr2005, Vol. 67 Issue 4, p1297 

    Plasminogen activator inhibitor-1 deficiency retards diabetic nephropathy.Background.Plasminogen activator inhibitor-1 (PAI-1) is increased in kidneys of humans and animals with diabetic nephropathy and is associated with extracellular matrix (ECM) accumulation. PAI-1 may promote ECM buildup by...

  • Norcantharidin inhibits the expression of extracellular matrix and TGF-β1 in HK-2 cells induced by high glucose independent of calcineurin signal pathway. Li, Ying; Chen, Qiong; Liu, Fu-You; Peng, You-Ming; Wang, Shuai; Li, Ji; Li, Jun; Duan, Shao-Bin; Sun, Lin; Ling, Guang-Hui; Luo, Jun-Hui // Laboratory Investigation (00236837);Dec2011, Vol. 91 Issue 12, p1706 

    Norcantharidin (NCTD) was shown in our previous studies to attenuate renal tubulointerstitial fibrosis in rat models with diabetic nephropathy (DN). The aim of this study was to determine the effects of NCTD on the expression of extracellular matrix (ECM) and TGF-β1 in HK-2 cells stimulated...

  • Combined effects of moderately elevated blood glucose and locally produced TGF-{beta}1 on glomerular morphology and renal collagen production. Søren Krag; Jens R. Nyengaard; Lise Wogensen // Nephrology Dialysis Transplantation;Sep2007, Vol. 22 Issue 9, p2485 

    Background. There is a correlation between renal graft rejection and blood glucose (BG) levels. Furthermore, diabetic patients may develop non-diabetic renal diseases, which in some circumstances progress rapidly. Since transforming growth factor-β1 (TGF-β) levels are elevated in many...

  • Expression of TGF-β–induced matrix protein βig-h3 is up-regulated in the diabetic rat kidney and human proximal tubular epithelial cells treated with high glucose. Lee, Suk-Hee; Bae, Jong-Sup; Park, Sun-Hee; Lee, Byung-Heon; Park, Rang-Woon; Choi, Je-Yong; Park, Jae Yong; Ha, Sung-Woo; Kim, Yong-Lim; Kwon, Tae-Hwan; Kim, In-San // Kidney International;Sep2003, Vol. 64 Issue 3, p1012 

    Expression of TGF-β–induced matrix protein βig-h3 is up-regulated in the diabetic rat kidney and human proximal tubular epithelial cells treated with high glucose. Backgrounds. βig-h3 is an extracellular matrix protein whose expression in several cell types is greatly increased...

  • Diagnosis, Pathology, and Pathophysiology.  // Kidney;Jan/Feb2002, Vol. 11 Issue 1, p11 

    Presents abstracts of studies related to the diagnosis, pathology and pathophysiology of kidney diseases. Evaluation of the sensitivity of cystatin C and creatinine in detecting early renal impairment in patients with diabetes; Effect of blocking angiotensin II synthesis on the preservation of...

  • Rosiglitazone Prevents Advanced Glycation End Products–Induced Renal Toxicity Likely through Suppression of Plasminogen Activator Inhibitor-1. Xiaoyan Yu; Cai Li; Xiaokun Li; Lu Cai // Toxicological Sciences;Apr2007, Vol. 96 Issue 2, p346 

    In the development of diabetic nephropathy, advanced glycation end products (AGEs) play a causative role via induction of extracellular matrix (ECM) accumulation. Plasminogen activator inhibitor-1 (PAI-1), as a major inhibitor of plasminogen activator that plays an important role in degrading...

  • Podocyte biology in diabetic nephropathy. Li, J. J.; Kwak, S. J.; Jung, D. S.; Kim, J.-J.; Yoo, T.-H.; Ryu, D.-R.; Han, S. H.; Choi, H. Y.; Lee, J. E.; Moon, S. J.; Kim, D. K.; Han, D. S.; Kang, S.-W. // Kidney International Supplement;Aug2007, Issue 106, p36 

    Glomerular visceral epithelial cells, namely podocytes, are highly specialized cells and give rise to primary processes, secondary processes, and finally foot processes. The foot processes of neighboring podocytes interdigitate, leaving between them filtration slits. These are bridged by an...

  • SPARC gene expression is reduced in early diabetes-related kidney growth. Gilbert, Richard E.; McNally, Paul G.; Cox, Alison; Dziadek, Marie; Rumble, Jon; Cooper, Mark E.; Jerums, George // Kidney International;Oct1995, Vol. 48 Issue 4, p1216 

    Renal enlargement is a characteristic feature of diabetes in humans and experimental animals that may predict subsequent renal disease. The biological processes involved in diabetes-related kidney growth are complex and involve changes in extracellular matrix, cell hypertrophy and hyperplasia....

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics