The role of transforming growth factor-beta/SMAD3 in the pathogenesis of metabolic syndrome.

Transforming growth factor-beta/SMAD3 signaling has been implicated in various metabolic processes. However, the systemic effects of SMAD3 deficiency on adiposity and insulin resistance remain obscure. We found that SMAD3-knockout mice exhibited diminished adiposity with improved glucose tolerance a...

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Main Author: Tan, Chek Kun.
Other Authors: Tan Nguan Soon
Format: Theses and Dissertations
Language:English
Published: 2013
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Online Access:http://hdl.handle.net/10356/52658
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-526582023-02-28T18:38:44Z The role of transforming growth factor-beta/SMAD3 in the pathogenesis of metabolic syndrome. Tan, Chek Kun. Tan Nguan Soon School of Biological Sciences DRNTU::Science Transforming growth factor-beta/SMAD3 signaling has been implicated in various metabolic processes. However, the systemic effects of SMAD3 deficiency on adiposity and insulin resistance remain obscure. We found that SMAD3-knockout mice exhibited diminished adiposity with improved glucose tolerance and insulin sensitivity and were resistant against the development of obesity and type 2 diabetes upon a high-fat diet challenge, suggesting that SMAD3 is a potential target for the treatment of obesity and its associated disorders. Moreover, recent studies reveal that patients carrying SMAD3 mutations developed a syndromic form of aortic aneurysms. Yet, the underlying mechanism leading to the pathogenesis of aortic aneurysms in these patients still remain elusive. We found that SMAD3-knockout mice developed aortic aneurysms when infused with angiotensin II, ultimately died from aortic rupture. The mechanism of these severe abnormalities involves an aberrant upregulation of nitric oxide (NO) production mediated by inducible NO synthase and an activation of matrix metalloproteinase-9. ​Doctor of Philosophy (SBS) 2013-05-21T09:04:15Z 2013-05-21T09:04:15Z 2013 2013 Thesis http://hdl.handle.net/10356/52658 en 254 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science
spellingShingle DRNTU::Science
Tan, Chek Kun.
The role of transforming growth factor-beta/SMAD3 in the pathogenesis of metabolic syndrome.
description Transforming growth factor-beta/SMAD3 signaling has been implicated in various metabolic processes. However, the systemic effects of SMAD3 deficiency on adiposity and insulin resistance remain obscure. We found that SMAD3-knockout mice exhibited diminished adiposity with improved glucose tolerance and insulin sensitivity and were resistant against the development of obesity and type 2 diabetes upon a high-fat diet challenge, suggesting that SMAD3 is a potential target for the treatment of obesity and its associated disorders. Moreover, recent studies reveal that patients carrying SMAD3 mutations developed a syndromic form of aortic aneurysms. Yet, the underlying mechanism leading to the pathogenesis of aortic aneurysms in these patients still remain elusive. We found that SMAD3-knockout mice developed aortic aneurysms when infused with angiotensin II, ultimately died from aortic rupture. The mechanism of these severe abnormalities involves an aberrant upregulation of nitric oxide (NO) production mediated by inducible NO synthase and an activation of matrix metalloproteinase-9.
author2 Tan Nguan Soon
author_facet Tan Nguan Soon
Tan, Chek Kun.
format Theses and Dissertations
author Tan, Chek Kun.
author_sort Tan, Chek Kun.
title The role of transforming growth factor-beta/SMAD3 in the pathogenesis of metabolic syndrome.
title_short The role of transforming growth factor-beta/SMAD3 in the pathogenesis of metabolic syndrome.
title_full The role of transforming growth factor-beta/SMAD3 in the pathogenesis of metabolic syndrome.
title_fullStr The role of transforming growth factor-beta/SMAD3 in the pathogenesis of metabolic syndrome.
title_full_unstemmed The role of transforming growth factor-beta/SMAD3 in the pathogenesis of metabolic syndrome.
title_sort role of transforming growth factor-beta/smad3 in the pathogenesis of metabolic syndrome.
publishDate 2013
url http://hdl.handle.net/10356/52658
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