NEDD4-1 deficiency impairs satellite cell function during skeletal muscle regeneration

Satellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell function and maintenance are regulated by extrinsic and intrinsic mechanisms, including the ubiquitin-proteasome system, which is key for maintaining protein homeosta...

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Published inBiological research Vol. 56; no. 1; p. 21
Main Authors Cabezas, Felipe, Cabello-Verrugio, Claudio, González, Natalia, Salas, Jeremy, Ramírez, Manuel J, de la Vega, Eduardo, Olguín, Hugo C
Format Journal Article
LanguageEnglish
Portuguese
Published England BioMed Central Ltd 05.05.2023
BioMed Central
Sociedad de Biología de Chile
BMC
Subjects
BIOLOGY
Cell Differentiation
Cell Proliferation - physiology
Enzymes
Fibroblasts
Homeostasis
Ligases
Muscle Development - physiology
Muscle differentiation
Muscle stem cells
Muscle, Skeletal - metabolism
Muscles
Musculoskeletal system
NEDD4-1
PAX7 Transcription Factor - genetics
PAX7 Transcription Factor - metabolism
Proteasome Endopeptidase Complex - metabolism
Proteasomes
Proteins
Satellite cells
Skeletal muscle
Skeletal muscle regeneration
Stem Cells
Ubiquitin
Ubiquitin-protein ligase
Ubiquitins - metabolism
Germany
Skeletal muscle regeneration
Satellite cells
NEDD4-1
Muscle differentiation
Muscle stem cells
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Abstract Satellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell function and maintenance are regulated by extrinsic and intrinsic mechanisms, including the ubiquitin-proteasome system, which is key for maintaining protein homeostasis. In this context, it has been shown that ubiquitin-ligase NEDD4-1 targets the transcription factor PAX7 for proteasome-dependent degradation, promoting muscle differentiation in vitro. Nonetheless, whether NEDD4-1 is required for satellite cell function in regenerating muscle remains to be determined. Using conditional gene ablation, we show that NEDD4-1 loss, specifically in the satellite cell population, impairs muscle regeneration resulting in a significant reduction of whole-muscle size. At the cellular level, NEDD4-1-null muscle progenitors exhibit a significant decrease in the ability to proliferate and differentiate, contributing to the formation of myofibers with reduced diameter. These results indicate that NEDD4-1 expression is critical for proper muscle regeneration in vivo and suggest that it may control satellite cell function at multiple levels.
AbstractList Abstract Background Satellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell function and maintenance are regulated by extrinsic and intrinsic mechanisms, including the ubiquitin–proteasome system, which is key for maintaining protein homeostasis. In this context, it has been shown that ubiquitin-ligase NEDD4-1 targets the transcription factor PAX7 for proteasome-dependent degradation, promoting muscle differentiation in vitro. Nonetheless, whether NEDD4-1 is required for satellite cell function in regenerating muscle remains to be determined. Results Using conditional gene ablation, we show that NEDD4-1 loss, specifically in the satellite cell population, impairs muscle regeneration resulting in a significant reduction of whole-muscle size. At the cellular level, NEDD4-1-null muscle progenitors exhibit a significant decrease in the ability to proliferate and differentiate, contributing to the formation of myofibers with reduced diameter. Conclusions These results indicate that NEDD4-1 expression is critical for proper muscle regeneration in vivo and suggest that it may control satellite cell function at multiple levels.
Satellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell function and maintenance are regulated by extrinsic and intrinsic mechanisms, including the ubiquitin-proteasome system, which is key for maintaining protein homeostasis. In this context, it has been shown that ubiquitin-ligase NEDD4-1 targets the transcription factor PAX7 for proteasome-dependent degradation, promoting muscle differentiation in vitro. Nonetheless, whether NEDD4-1 is required for satellite cell function in regenerating muscle remains to be determined. Using conditional gene ablation, we show that NEDD4-1 loss, specifically in the satellite cell population, impairs muscle regeneration resulting in a significant reduction of whole-muscle size. At the cellular level, NEDD4-1-null muscle progenitors exhibit a significant decrease in the ability to proliferate and differentiate, contributing to the formation of myofibers with reduced diameter. These results indicate that NEDD4-1 expression is critical for proper muscle regeneration in vivo and suggest that it may control satellite cell function at multiple levels.
BackgroundSatellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell function and maintenance are regulated by extrinsic and intrinsic mechanisms, including the ubiquitin–proteasome system, which is key for maintaining protein homeostasis. In this context, it has been shown that ubiquitin-ligase NEDD4-1 targets the transcription factor PAX7 for proteasome-dependent degradation, promoting muscle differentiation in vitro. Nonetheless, whether NEDD4-1 is required for satellite cell function in regenerating muscle remains to be determined.ResultsUsing conditional gene ablation, we show that NEDD4-1 loss, specifically in the satellite cell population, impairs muscle regeneration resulting in a significant reduction of whole-muscle size. At the cellular level, NEDD4-1-null muscle progenitors exhibit a significant decrease in the ability to proliferate and differentiate, contributing to the formation of myofibers with reduced diameter.ConclusionsThese results indicate that NEDD4-1 expression is critical for proper muscle regeneration in vivo and suggest that it may control satellite cell function at multiple levels.
Satellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell function and maintenance are regulated by extrinsic and intrinsic mechanisms, including the ubiquitin-proteasome system, which is key for maintaining protein homeostasis. In this context, it has been shown that ubiquitin-ligase NEDD4-1 targets the transcription factor PAX7 for proteasome-dependent degradation, promoting muscle differentiation in vitro. Nonetheless, whether NEDD4-1 is required for satellite cell function in regenerating muscle remains to be determined. Using conditional gene ablation, we show that NEDD4-1 loss, specifically in the satellite cell population, impairs muscle regeneration resulting in a significant reduction of whole-muscle size. At the cellular level, NEDD4-1-null muscle progenitors exhibit a significant decrease in the ability to proliferate and differentiate, contributing to the formation of myofibers with reduced diameter. These results indicate that NEDD4-1 expression is critical for proper muscle regeneration in vivo and suggest that it may control satellite cell function at multiple levels.
Abstract Background Satellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell function and maintenance are regulated by extrinsic and intrinsic mechanisms, including the ubiquitin–proteasome system, which is key for maintaining protein homeostasis. In this context, it has been shown that ubiquitin-ligase NEDD4-1 targets the transcription factor PAX7 for proteasome-dependent degradation, promoting muscle differentiation in vitro. Nonetheless, whether NEDD4-1 is required for satellite cell function in regenerating muscle remains to be determined. Results Using conditional gene ablation, we show that NEDD4-1 loss, specifically in the satellite cell population, impairs muscle regeneration resulting in a significant reduction of whole-muscle size. At the cellular level, NEDD4-1-null muscle progenitors exhibit a significant decrease in the ability to proliferate and differentiate, contributing to the formation of myofibers with reduced diameter. Conclusions These results indicate that NEDD4-1 expression is critical for proper muscle regeneration in vivo and suggest that it may control satellite cell function at multiple levels.
Background Satellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell function and maintenance are regulated by extrinsic and intrinsic mechanisms, including the ubiquitin-proteasome system, which is key for maintaining protein homeostasis. In this context, it has been shown that ubiquitin-ligase NEDD4-1 targets the transcription factor PAX7 for proteasome-dependent degradation, promoting muscle differentiation in vitro. Nonetheless, whether NEDD4-1 is required for satellite cell function in regenerating muscle remains to be determined. Results Using conditional gene ablation, we show that NEDD4-1 loss, specifically in the satellite cell population, impairs muscle regeneration resulting in a significant reduction of whole-muscle size. At the cellular level, NEDD4-1-null muscle progenitors exhibit a significant decrease in the ability to proliferate and differentiate, contributing to the formation of myofibers with reduced diameter. Conclusions These results indicate that NEDD4-1 expression is critical for proper muscle regeneration in vivo and suggest that it may control satellite cell function at multiple levels. Keywords: Skeletal muscle regeneration, Muscle differentiation, Satellite cells, NEDD4-1, Muscle stem cells
ArticleNumber 21
Audience Academic
Author Salas, Jeremy
González, Natalia
de la Vega, Eduardo
Cabezas, Felipe
Cabello-Verrugio, Claudio
Ramírez, Manuel J
Olguín, Hugo C
AuthorAffiliation Universidad Andres Bello
Pontificia Universidad Católica de Chile
Universidad San Sebastián
AuthorAffiliation_xml – name: Universidad Andres Bello
– name: Universidad San Sebastián
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  givenname: Claudio
  surname: Cabello-Verrugio
  fullname: Cabello-Verrugio, Claudio
  organization: Millennium Institute on Immunology and Immunotherapy, Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile
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  givenname: Natalia
  surname: González
  fullname: González, Natalia
  organization: Laboratory of Tissue Repair and Adult Stem Cells, Molecular and Cell Biology Department, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile
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  givenname: Jeremy
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  givenname: Manuel J
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  givenname: Eduardo
  surname: de la Vega
  fullname: de la Vega, Eduardo
  organization: Laboratory of Tissue Repair and Adult Stem Cells, Molecular and Cell Biology Department, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile
– sequence: 7
  givenname: Hugo C
  orcidid: 0000-0003-4072-7776
  surname: Olguín
  fullname: Olguín, Hugo C
  email: holguin@bio.puc.cl
  organization: Laboratory of Tissue Repair and Adult Stem Cells, Molecular and Cell Biology Department, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile. holguin@bio.puc.cl
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Issue 1
Keywords Skeletal muscle regeneration
Satellite cells
NEDD4-1
Muscle differentiation
Muscle stem cells
Language English
Portuguese
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SSID ssj0025026
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Snippet Satellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell function and maintenance...
Abstract Background Satellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell...
Background Satellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell function and...
BackgroundSatellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell function and...
BACKGROUNDSatellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell function and...
Abstract Background Satellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell...
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StartPage 21
SubjectTerms BIOLOGY
Cell Differentiation
Cell Proliferation - physiology
Enzymes
Fibroblasts
Homeostasis
Ligases
Muscle Development - physiology
Muscle differentiation
Muscle stem cells
Muscle, Skeletal - metabolism
Muscles
Musculoskeletal system
NEDD4-1
PAX7 Transcription Factor - genetics
PAX7 Transcription Factor - metabolism
Proteasome Endopeptidase Complex - metabolism
Proteasomes
Proteins
Satellite cells
Skeletal muscle
Skeletal muscle regeneration
Stem Cells
Ubiquitin
Ubiquitin-protein ligase
Ubiquitins - metabolism
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Title NEDD4-1 deficiency impairs satellite cell function during skeletal muscle regeneration
URI https://www.ncbi.nlm.nih.gov/pubmed/37147738
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https://search.proquest.com/docview/2810917689
https://pubmed.ncbi.nlm.nih.gov/PMC10161651
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