Premium
Alcohol Differentially Alters Extracellular Matrix and Adhesion Molecule Expression in Skeletal Muscle and Heart
Author(s) -
Steiner Jennifer L.,
Pruznak Anne M.,
Navaratnarajah Maithili,
Lang Charles H.
Publication year - 2015
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12771
Subject(s) - extracellular matrix , skeletal muscle , laminin , gene expression , western blot , medicine , endocrinology , cell adhesion molecule , biology , fibrosis , messenger rna , gastrocnemius muscle , microbiology and biotechnology , chemistry , biochemistry , gene
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 m RNA 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 m RNA and/or protein for collagens α 1(I), α 2(I), α 1( III ), and α 2( 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 m RNA and protein content for other ECM components, such as integrin‐ α 5, L‐selectin, PECAM , SPARC, and ADAMTS2, were also increased by alcohol. Only laminin‐ α 3 m RNA was decreased in gastrocnemius from alcohol‐fed rats, while 66 ECM ‐ or cell adhesion‐related m RNA s were unchanged by alcohol. For heart, expression of 16 genes was up‐regulated, expression of 3 genes was down‐regulated, and 65 m RNA s 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 m RNA in both skeletal and cardiac muscle, but IL ‐6 m RNA was increased and IL ‐10 m RNA 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.