Alcohol Differentially Alters Extracellular Matrix and Adhesion Molecule Expression in Skeletal Muscle and Heart

Jennifer L. Steiner, Anne M. Pruznak, Maithili Navaratnarajah, Charles H. Lang

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: The production of fibrosis in response to chronic alcohol abuse is well recognized in liver but has not been fully characterized in striated muscle and may contribute to functional impairment. Therefore, the purpose of this study was to use an unbiased discovery-based approach to determine the effect of chronic alcohol consumption on the expression profile of genes important for cell-cell and cell-extracellular matrix (ECM) interactions in both skeletal and cardiac muscle. Methods: Adult male rats were pair-fed an alcohol-containing liquid diet or control diet for 24 weeks, and skeletal muscle (gastrocnemius) and heart were collected in the freely fed state. A pathway-focused gene expression polymerase chain reaction array was performed on these tissues to assess mRNA content for 84 ECM proteins, and selected proteins were confirmed by Western blot analysis. Results: In gastrocnemius, alcohol feeding up-regulated the expression of 11 genes and down-regulated the expression of 1 gene. Alcohol increased fibrosis as indicated by increased mRNA and/or protein for collagens α1(I), α2(I), α1(III), and α2(IV) as well as hydroxyproline. Alcohol also increased α-smooth muscle actin protein, an index of myofibroblast activation, but no concomitant change in transforming growth factor-β was detected. The mRNA and protein content for other ECM components, such as integrin-α5, L-selectin, PECAM, SPARC, and ADAMTS2, were also increased by alcohol. Only laminin-α3 mRNA was decreased in gastrocnemius from alcohol-fed rats, while 66 ECM- or cell adhesion-related mRNAs were unchanged by alcohol. For heart, expression of 16 genes was up-regulated, expression of 3 genes was down-regulated, and 65 mRNAs were unchanged by alcohol; there were no common alcohol-induced gene expression changes between heart and skeletal muscle. Finally, alcohol increased tumor necrosis factor-α and interleukin (IL)-12 mRNA in both skeletal and cardiac muscle, but IL-6 mRNA was increased and IL-10 mRNA decreased only in skeletal muscle. Conclusions: These data demonstrate a fibrotic response in striated muscle from chronic alcohol-fed rats which is tissue specific in nature, suggesting different regulatory mechanisms.

Original languageEnglish (US)
Pages (from-to)1330-1340
Number of pages11
JournalAlcoholism: Clinical and Experimental Research
Volume39
Issue number8
DOIs
StatePublished - Aug 1 2015

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Extracellular Matrix
Muscle
Skeletal Muscle
Adhesion
Alcohols
Molecules
Messenger RNA
Gene Expression
Genes
Myocardium
Striated Muscle
Rats
Nutrition
Gene expression
Fibrosis
Proteins
Diet
L-Selectin
Tissue
Myofibroblasts

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

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title = "Alcohol Differentially Alters Extracellular Matrix and Adhesion Molecule Expression in Skeletal Muscle and Heart",
abstract = "Background: The production of fibrosis in response to chronic alcohol abuse is well recognized in liver but has not been fully characterized in striated muscle and may contribute to functional impairment. Therefore, the purpose of this study was to use an unbiased discovery-based approach to determine the effect of chronic alcohol consumption on the expression profile of genes important for cell-cell and cell-extracellular matrix (ECM) interactions in both skeletal and cardiac muscle. Methods: Adult male rats were pair-fed an alcohol-containing liquid diet or control diet for 24 weeks, and skeletal muscle (gastrocnemius) and heart were collected in the freely fed state. A pathway-focused gene expression polymerase chain reaction array was performed on these tissues to assess mRNA content for 84 ECM proteins, and selected proteins were confirmed by Western blot analysis. Results: In gastrocnemius, alcohol feeding up-regulated the expression of 11 genes and down-regulated the expression of 1 gene. Alcohol increased fibrosis as indicated by increased mRNA and/or protein for collagens α1(I), α2(I), α1(III), and α2(IV) as well as hydroxyproline. Alcohol also increased α-smooth muscle actin protein, an index of myofibroblast activation, but no concomitant change in transforming growth factor-β was detected. The mRNA and protein content for other ECM components, such as integrin-α5, L-selectin, PECAM, SPARC, and ADAMTS2, were also increased by alcohol. Only laminin-α3 mRNA was decreased in gastrocnemius from alcohol-fed rats, while 66 ECM- or cell adhesion-related mRNAs were unchanged by alcohol. For heart, expression of 16 genes was up-regulated, expression of 3 genes was down-regulated, and 65 mRNAs were unchanged by alcohol; there were no common alcohol-induced gene expression changes between heart and skeletal muscle. Finally, alcohol increased tumor necrosis factor-α and interleukin (IL)-12 mRNA in both skeletal and cardiac muscle, but IL-6 mRNA was increased and IL-10 mRNA decreased only in skeletal muscle. Conclusions: These data demonstrate a fibrotic response in striated muscle from chronic alcohol-fed rats which is tissue specific in nature, suggesting different regulatory mechanisms.",
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Alcohol Differentially Alters Extracellular Matrix and Adhesion Molecule Expression in Skeletal Muscle and Heart. / Steiner, Jennifer L.; Pruznak, Anne M.; Navaratnarajah, Maithili; Lang, Charles H.

In: Alcoholism: Clinical and Experimental Research, Vol. 39, No. 8, 01.08.2015, p. 1330-1340.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Alcohol Differentially Alters Extracellular Matrix and Adhesion Molecule Expression in Skeletal Muscle and Heart

AU - Steiner, Jennifer L.

AU - Pruznak, Anne M.

AU - Navaratnarajah, Maithili

AU - Lang, Charles H.

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N2 - Background: The production of fibrosis in response to chronic alcohol abuse is well recognized in liver but has not been fully characterized in striated muscle and may contribute to functional impairment. Therefore, the purpose of this study was to use an unbiased discovery-based approach to determine the effect of chronic alcohol consumption on the expression profile of genes important for cell-cell and cell-extracellular matrix (ECM) interactions in both skeletal and cardiac muscle. Methods: Adult male rats were pair-fed an alcohol-containing liquid diet or control diet for 24 weeks, and skeletal muscle (gastrocnemius) and heart were collected in the freely fed state. A pathway-focused gene expression polymerase chain reaction array was performed on these tissues to assess mRNA content for 84 ECM proteins, and selected proteins were confirmed by Western blot analysis. Results: In gastrocnemius, alcohol feeding up-regulated the expression of 11 genes and down-regulated the expression of 1 gene. Alcohol increased fibrosis as indicated by increased mRNA and/or protein for collagens α1(I), α2(I), α1(III), and α2(IV) as well as hydroxyproline. Alcohol also increased α-smooth muscle actin protein, an index of myofibroblast activation, but no concomitant change in transforming growth factor-β was detected. The mRNA and protein content for other ECM components, such as integrin-α5, L-selectin, PECAM, SPARC, and ADAMTS2, were also increased by alcohol. Only laminin-α3 mRNA was decreased in gastrocnemius from alcohol-fed rats, while 66 ECM- or cell adhesion-related mRNAs were unchanged by alcohol. For heart, expression of 16 genes was up-regulated, expression of 3 genes was down-regulated, and 65 mRNAs were unchanged by alcohol; there were no common alcohol-induced gene expression changes between heart and skeletal muscle. Finally, alcohol increased tumor necrosis factor-α and interleukin (IL)-12 mRNA in both skeletal and cardiac muscle, but IL-6 mRNA was increased and IL-10 mRNA decreased only in skeletal muscle. Conclusions: These data demonstrate a fibrotic response in striated muscle from chronic alcohol-fed rats which is tissue specific in nature, suggesting different regulatory mechanisms.

AB - Background: The production of fibrosis in response to chronic alcohol abuse is well recognized in liver but has not been fully characterized in striated muscle and may contribute to functional impairment. Therefore, the purpose of this study was to use an unbiased discovery-based approach to determine the effect of chronic alcohol consumption on the expression profile of genes important for cell-cell and cell-extracellular matrix (ECM) interactions in both skeletal and cardiac muscle. Methods: Adult male rats were pair-fed an alcohol-containing liquid diet or control diet for 24 weeks, and skeletal muscle (gastrocnemius) and heart were collected in the freely fed state. A pathway-focused gene expression polymerase chain reaction array was performed on these tissues to assess mRNA content for 84 ECM proteins, and selected proteins were confirmed by Western blot analysis. Results: In gastrocnemius, alcohol feeding up-regulated the expression of 11 genes and down-regulated the expression of 1 gene. Alcohol increased fibrosis as indicated by increased mRNA and/or protein for collagens α1(I), α2(I), α1(III), and α2(IV) as well as hydroxyproline. Alcohol also increased α-smooth muscle actin protein, an index of myofibroblast activation, but no concomitant change in transforming growth factor-β was detected. The mRNA and protein content for other ECM components, such as integrin-α5, L-selectin, PECAM, SPARC, and ADAMTS2, were also increased by alcohol. Only laminin-α3 mRNA was decreased in gastrocnemius from alcohol-fed rats, while 66 ECM- or cell adhesion-related mRNAs were unchanged by alcohol. For heart, expression of 16 genes was up-regulated, expression of 3 genes was down-regulated, and 65 mRNAs were unchanged by alcohol; there were no common alcohol-induced gene expression changes between heart and skeletal muscle. Finally, alcohol increased tumor necrosis factor-α and interleukin (IL)-12 mRNA in both skeletal and cardiac muscle, but IL-6 mRNA was increased and IL-10 mRNA decreased only in skeletal muscle. Conclusions: These data demonstrate a fibrotic response in striated muscle from chronic alcohol-fed rats which is tissue specific in nature, suggesting different regulatory mechanisms.

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