Reversal of Renal Fibrosis, Inflammation, and Glomerular Hypertrophy by Kallikrein Gene Delivery

2006 ◽  
Vol 17 (5) ◽  
pp. 545-555 ◽  
Author(s):  
Grant Bledsoe ◽  
Bo Shen ◽  
Yuyu Yao ◽  
Jenny J. Zhang ◽  
Lee Chao ◽  
...  

2006 ◽  
Vol 0 (0) ◽  
pp. 060801084750016
Author(s):  
Grant Bledsoe ◽  
Bo Shen ◽  
Yuyu Yao ◽  
Jenny J. Zhang ◽  
Lee Chao ◽  
...  


2005 ◽  
Vol 289 (3) ◽  
pp. F622-F631 ◽  
Author(s):  
Chun-Fang Xia ◽  
Grant Bledsoe ◽  
Lee Chao ◽  
Julie Chao

In DOCA-salt hypertension, renal kallikrein levels are increased and may play a protective role in renal injury. We investigated the effect of enhanced kallikrein levels on kidney remodeling of DOCA-salt hypertensive rats by systemic delivery of adenovirus containing human tissue kallikrein gene. Recombinant human kallikrein was detected in the urine and serum of rats after gene delivery. Kallikrein gene transfer significantly decreased DOCA- and salt-induced proteinuria, glomerular sclerosis, tubular dilatation, and luminal protein casts. Sirius red staining showed that kallikrein gene transfer reduced renal fibrosis, which was confirmed by decreased collagen I and fibronectin levels. Furthermore, kallikrein gene delivery diminished myofibroblast accumulation in the interstitium of the cortex and medulla, as well as transforming growth factor (TGF)-β1 immunostaining in glomeruli. Western blot analysis and ELISA verified the decrease in immunoreactive TGF-β1 levels. Kallikrein gene transfer also significantly reduced kidney weight, glomerular size, proliferating tubular epithelial cells, and macrophages/monocytes. Reduction of proliferation and hypertrophy was associated with reduced levels of the cyclin-dependent kinase inhibitor p27Kip1, and the phosphorylation of c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). The protective effects of kallikrein were accompanied by increased urinary nitrate/nitrite and cGMP levels, and suppression of superoxide formation. These results indicate that kallikrein protects against mineralocorticoid-induced renal fibrosis glomerular hypertrophy, and renal cell proliferation via inhibition of oxidative stress, JNK/ERK activation, and p27Kip1 and TGF-β1 expression.



2006 ◽  
Vol 175 (4S) ◽  
pp. 323-324 ◽  
Author(s):  
Joseph Dall'era ◽  
Sweaty Koul ◽  
Jesse Mills ◽  
Jeremy Myers ◽  
Randall B. Meacham ◽  
...  


1990 ◽  
Vol 79 (1) ◽  
pp. 135-139
Author(s):  
Andrew N. Binns
Keyword(s):  


2007 ◽  
Author(s):  
Gregory T Zugates ◽  
Weidan Peng ◽  
Andreas Zumbuehl ◽  
Siddharth Jhunjhunwala ◽  
Yu-Hung Huang ◽  
...  
Keyword(s):  


2011 ◽  
Vol 59 (S 01) ◽  
Author(s):  
Y Zhang ◽  
W Li ◽  
W Wang ◽  
L Ou ◽  
A Liebold ◽  
...  


2012 ◽  
Vol 60 (S 01) ◽  
Author(s):  
H Brinks ◽  
S Longnus ◽  
T Carrel ◽  
J Rabinowitz ◽  
WJ Koch ◽  
...  


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