Lack of Smad3 signaling leads to impaired skeletal muscle regeneration

Smad3 is a key intracellular signaling mediator for both transforming growth factor-β and myostatin, two major regulators of skeletal muscle growth. Previous published work has revealed pronounced muscle atrophy together with impaired satellite cell functionality in Smad3-null muscles. In the presen...

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Main Authors: Sharma, Mridula, McFarlane, Craig, Wahli, Walter, Ge, Xiaojia, Vajjala, Anuradha, Kambadur, Ravi
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2013
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Online Access:https://hdl.handle.net/10356/98518
http://hdl.handle.net/10220/12445
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-985182020-03-07T12:18:20Z Lack of Smad3 signaling leads to impaired skeletal muscle regeneration Sharma, Mridula McFarlane, Craig Wahli, Walter Ge, Xiaojia Vajjala, Anuradha Kambadur, Ravi School of Biological Sciences DRNTU::Science::Biological sciences Smad3 is a key intracellular signaling mediator for both transforming growth factor-β and myostatin, two major regulators of skeletal muscle growth. Previous published work has revealed pronounced muscle atrophy together with impaired satellite cell functionality in Smad3-null muscles. In the present study, we have further validated a role for Smad3 signaling in skeletal muscle regeneration. Here, we show that Smad3-null mice had incomplete recovery of muscle weight and myofiber size after muscle injury. Histological/immunohistochemical analysis suggested impaired inflammatory response and reduced number of activated myoblasts during the early stages of muscle regeneration in the tibialis anterior muscle of Smad3-null mice. Nascent myofibers formed after muscle injury were also reduced in number. Moreover, Smad3-null regenerated muscle had decreased oxidative enzyme activity and impaired mitochondrial biogenesis, evident by the downregulation of the gene encoding mitochondrial transcription factor A, a master regulator of mitochondrial biogenesis. Consistent with known Smad3 function, reduced fibrotic tissue formation was also seen in regenerated Smad3-null muscle. In conclusion, Smad3 deficiency leads to impaired muscle regeneration, which underscores an essential role of Smad3 in postnatal myogenesis. Given the negative role of myostatin during muscle regeneration, the increased expression of myostatin observed in Smad3-null muscle may contribute to the regeneration defects. 2013-07-29T04:46:46Z 2019-12-06T19:56:25Z 2013-07-29T04:46:46Z 2019-12-06T19:56:25Z 2012 2012 Journal Article Ge, X., Vajjala, A., McFarlane, C., Wahli, W., Sharma, M., & Kambadur, R. (2012). Lack of Smad3 signaling leads to impaired skeletal muscle regeneration. American Journal of Physiology: Endocrinology and Metabolism, 303(1), E90-E102. https://hdl.handle.net/10356/98518 http://hdl.handle.net/10220/12445 10.1152/ajpendo.00113.2012 en American journal of physiology : endocrinology and metabolism. © 2012 The American Physiological Society.
institution Nanyang Technological University
building NTU Library
country Singapore
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences
spellingShingle DRNTU::Science::Biological sciences
Sharma, Mridula
McFarlane, Craig
Wahli, Walter
Ge, Xiaojia
Vajjala, Anuradha
Kambadur, Ravi
Lack of Smad3 signaling leads to impaired skeletal muscle regeneration
description Smad3 is a key intracellular signaling mediator for both transforming growth factor-β and myostatin, two major regulators of skeletal muscle growth. Previous published work has revealed pronounced muscle atrophy together with impaired satellite cell functionality in Smad3-null muscles. In the present study, we have further validated a role for Smad3 signaling in skeletal muscle regeneration. Here, we show that Smad3-null mice had incomplete recovery of muscle weight and myofiber size after muscle injury. Histological/immunohistochemical analysis suggested impaired inflammatory response and reduced number of activated myoblasts during the early stages of muscle regeneration in the tibialis anterior muscle of Smad3-null mice. Nascent myofibers formed after muscle injury were also reduced in number. Moreover, Smad3-null regenerated muscle had decreased oxidative enzyme activity and impaired mitochondrial biogenesis, evident by the downregulation of the gene encoding mitochondrial transcription factor A, a master regulator of mitochondrial biogenesis. Consistent with known Smad3 function, reduced fibrotic tissue formation was also seen in regenerated Smad3-null muscle. In conclusion, Smad3 deficiency leads to impaired muscle regeneration, which underscores an essential role of Smad3 in postnatal myogenesis. Given the negative role of myostatin during muscle regeneration, the increased expression of myostatin observed in Smad3-null muscle may contribute to the regeneration defects.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Sharma, Mridula
McFarlane, Craig
Wahli, Walter
Ge, Xiaojia
Vajjala, Anuradha
Kambadur, Ravi
format Article
author Sharma, Mridula
McFarlane, Craig
Wahli, Walter
Ge, Xiaojia
Vajjala, Anuradha
Kambadur, Ravi
author_sort Sharma, Mridula
title Lack of Smad3 signaling leads to impaired skeletal muscle regeneration
title_short Lack of Smad3 signaling leads to impaired skeletal muscle regeneration
title_full Lack of Smad3 signaling leads to impaired skeletal muscle regeneration
title_fullStr Lack of Smad3 signaling leads to impaired skeletal muscle regeneration
title_full_unstemmed Lack of Smad3 signaling leads to impaired skeletal muscle regeneration
title_sort lack of smad3 signaling leads to impaired skeletal muscle regeneration
publishDate 2013
url https://hdl.handle.net/10356/98518
http://hdl.handle.net/10220/12445
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