- About
-
The Global ETD Search service is a free service for researchers
to find electronic theses and dissertations. This service is
provided by the
Networked Digital Library of Theses and Dissertations.
Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
Search results
Showing 1 to 6 of 6 (0.01 seconds)| 1 |
The Role of Angiotensin-(1-7) in a Mouse Model of Renal FibrosisZimmerman, Danielle 22 January 2013 (has links)
Angiotensin-(1-7) [Ang-(1-7)] is a heptapeptide component of the renin angiotensin system and the endogenous ligand for the Mas receptor. Ang-(1-7) is generated mainly via angiotensin converting enzyme 2 (ACE2)-dependent cleavage of Angiotensin (Ang) II. Studies suggest Ang-(1-7) may protect against progression of renal injury in experimental models of chronic kidney disease, although the responses may be dose dependent. The role of Ang-(1-7) in the progression of renal fibrosis in unilateral ureteral obstruction (UUO) remains unclear. We tested the hypothesis that endogenous Ang-(1-7) and low dose exogenous Ang-(1-7) would protect against renal injury in the UUO model, while high dose Ang-(1-7) would exacerbate renal injury. Male C57Bl/6 mice underwent UUO and received vehicle, the Ang-(1-7) antagonist A779, or one of three doses of Ang-(1-7) for 10 days. Treatment with A779 exacerbated renal injury as seen by increased fibronectin, transforming growth factor-β (TGF-β), and α-smooth muscle actin (α-SMA) expression, increased tubulointerstitial fibrosis scores, macrophage infiltration, apoptosis, and NADPH oxidase activity in obstructed kidneys. Paradoxically, delivery of exogenous Ang-(1-7) was associated with increased renal injury regardless of dose. Taken together, these data indicate the Mas receptor may be sensitive to concentrations of Ang-(1-7) within the obstructed kidney and that exogenous Ang-(1-7) stimulates pro-fibrotic and pro-inflammatory signalling through unclear pathways.
|
| 2 |
The Role of Angiotensin-(1-7) in a Mouse Model of Renal FibrosisZimmerman, Danielle 22 January 2013 (has links)
Angiotensin-(1-7) [Ang-(1-7)] is a heptapeptide component of the renin angiotensin system and the endogenous ligand for the Mas receptor. Ang-(1-7) is generated mainly via angiotensin converting enzyme 2 (ACE2)-dependent cleavage of Angiotensin (Ang) II. Studies suggest Ang-(1-7) may protect against progression of renal injury in experimental models of chronic kidney disease, although the responses may be dose dependent. The role of Ang-(1-7) in the progression of renal fibrosis in unilateral ureteral obstruction (UUO) remains unclear. We tested the hypothesis that endogenous Ang-(1-7) and low dose exogenous Ang-(1-7) would protect against renal injury in the UUO model, while high dose Ang-(1-7) would exacerbate renal injury. Male C57Bl/6 mice underwent UUO and received vehicle, the Ang-(1-7) antagonist A779, or one of three doses of Ang-(1-7) for 10 days. Treatment with A779 exacerbated renal injury as seen by increased fibronectin, transforming growth factor-β (TGF-β), and α-smooth muscle actin (α-SMA) expression, increased tubulointerstitial fibrosis scores, macrophage infiltration, apoptosis, and NADPH oxidase activity in obstructed kidneys. Paradoxically, delivery of exogenous Ang-(1-7) was associated with increased renal injury regardless of dose. Taken together, these data indicate the Mas receptor may be sensitive to concentrations of Ang-(1-7) within the obstructed kidney and that exogenous Ang-(1-7) stimulates pro-fibrotic and pro-inflammatory signalling through unclear pathways.
|
| 3 |
The Role of Angiotensin-(1-7) in a Mouse Model of Renal FibrosisZimmerman, Danielle January 2013 (has links)
Angiotensin-(1-7) [Ang-(1-7)] is a heptapeptide component of the renin angiotensin system and the endogenous ligand for the Mas receptor. Ang-(1-7) is generated mainly via angiotensin converting enzyme 2 (ACE2)-dependent cleavage of Angiotensin (Ang) II. Studies suggest Ang-(1-7) may protect against progression of renal injury in experimental models of chronic kidney disease, although the responses may be dose dependent. The role of Ang-(1-7) in the progression of renal fibrosis in unilateral ureteral obstruction (UUO) remains unclear. We tested the hypothesis that endogenous Ang-(1-7) and low dose exogenous Ang-(1-7) would protect against renal injury in the UUO model, while high dose Ang-(1-7) would exacerbate renal injury. Male C57Bl/6 mice underwent UUO and received vehicle, the Ang-(1-7) antagonist A779, or one of three doses of Ang-(1-7) for 10 days. Treatment with A779 exacerbated renal injury as seen by increased fibronectin, transforming growth factor-β (TGF-β), and α-smooth muscle actin (α-SMA) expression, increased tubulointerstitial fibrosis scores, macrophage infiltration, apoptosis, and NADPH oxidase activity in obstructed kidneys. Paradoxically, delivery of exogenous Ang-(1-7) was associated with increased renal injury regardless of dose. Taken together, these data indicate the Mas receptor may be sensitive to concentrations of Ang-(1-7) within the obstructed kidney and that exogenous Ang-(1-7) stimulates pro-fibrotic and pro-inflammatory signalling through unclear pathways.
|
| 4 |
In Vivo Inhibition of TRPC6 by SH045 Attenuates Renal Fibrosis in a New Zealand Obese (NZO) Mouse Model of Metabolic SyndromeZheng, Zhihuang, Xu, Yao, Krügel, Ute, Schaefer, Michael, Grune, Tilman, Nürnberg, Bernd, Köhler, May-Britt, Gollasch, Maik, Tsvetkov, Dmitry, Marko, Lajos 02 February 2024 (has links)
Metabolic syndrome is a significant worldwide public health challenge and is inextricably
linked to adverse renal and cardiovascular outcomes. The inhibition of the transient receptor potential
cation channel subfamily C member 6 (TRPC6) has been found to ameliorate renal outcomes in the
unilateral ureteral obstruction (UUO) of accelerated renal fibrosis. Therefore, the pharmacological inhibition
of TPRC6 could be a promising therapeutic intervention in the progressive tubulo-interstitial
fibrosis in hypertension and metabolic syndrome. In the present study, we hypothesized that the
novel selective TRPC6 inhibitor SH045 (larixyl N-methylcarbamate) ameliorates UUO-accelerated
renal fibrosis in a New Zealand obese (NZO) mouse model, which is a polygenic model of metabolic
syndrome. The in vivo inhibition of TRPC6 by SH045 markedly decreased the mRNA expression of
pro-fibrotic markers (Col1a1, Col3a1, Col4a1, Acta2, Ccn2, Fn1) and chemokines (Cxcl1, Ccl5, Ccr2) in
UUO kidneys of NZO mice compared to kidneys of vehicle-treated animals. Renal expressions of
intercellular adhesion molecule 1 (ICAM-1) and -smooth muscle actin (-SMA) were diminished in
SH045- versus vehicle-treated UUO mice. Furthermore, renal inflammatory cell infiltration (F4/80+
and CD4+) and tubulointerstitial fibrosis (Sirius red and fibronectin staining) were ameliorated
in SH045-treated NZO mice. We conclude that the pharmacological inhibition of TRPC6 might
be a promising antifibrotic therapeutic method to treat progressive tubulo-interstitial fibrosis in
hypertension and metabolic syndrome.
|
| 5 |
THE ROLE OF STEROL REGULATORY ELEMENT BINDING PROTEIN (SREBP) IN KIDNEY FIBROSISMustafa, Maria 20 December 2015 (has links)
<p>There has been a steady increase in the number of patients with chronic kidney disease. The etiology has been linked to excessive fibrosis progression until the kidney function becomes compromised. We are investigating tubulointerstitial fibrosis (TIF) specifically, as it correlates strongly with the decline of renal function.</p> <p>In our study we investigated the role that active SREBP may play in apoptosis and fibrosis in vivo and in vitro. Treating HK-2 cells with TNFα resulted in the cleavage of SREBP and activation of its SRE promoter. By utilizing a number of inhibitors, we found TNFα induced SREBP cleavage through both a caspase independent and dependent manner.</p> <p>We used fatostatin, a SCAP inhibitor, to reduce the amount of active SREBP in animals in the unilateral ureter obstruction (UUO) model. This model is well known for its development of TIF. Fatostatin decreased SREBP-1 and SREBP-2 activation in mice after 7 and 14 days. Fatostatin increased glomerulotubular integrity and proximal tubular mass as evaluated using lectin staining, along with reducing the number of cells undergoing apoptosis as evaluated by TUNEL staining. Using the Masson Trichrome, Picrosirius red and fibronectin staining, we found a reduction of fibrosis. Fatostatin was also found to attenuate the accumulation of infiltrating myofibroblasts and T cells. These results point to a pathological role for SREBP in TIF.</p> / Master of Health Sciences (MSc)
|
| 6 |
Die Rolle des FK506 bei der Expression des BMP-Rezeptors BMPR1A / The role of FK506 during the expression of the BMP-Receptor BMPR1AKlöpper, Friederike 24 April 2017 (has links)
No description available.
|
Page generated in 0.0152 seconds