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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-toledo14618609582021-08-03T06:35:59Z ICAM-1 in Skeletal Muscle Disease and Regeneration Torres-Palsa, Maria Jose Physiology Biology Kinesiology ICAM-1 skeletal muscle regeneration mdx inflammatory response adhesion molecule muscle injury Skeletal muscle tissue has the unique ability to restore its structure and function after sustaining trauma and disease. The primary purpose of this research dissertation is to gain insight into the interactions between skeletal muscle regeneration and ICAM-1, an important protein of the inflammatory process and primary ligand for myeloid cells. The present study uses two murine models to characterize the expression and localization of ICAM-1 in skeletal muscle disease and regeneration. First, the hypothesis that ICAM-1 is expressed by myofibers and myeloid cells in dystrophin-deficient mice was tested. In muscles from Duchenne muscular dystrophy (mdx) mice, western blot revealed increased expression of ICAM-1 compared to control. ICAM-1 was expressed on the membrane of necrotic, injured, and regenerating myofibers and by CD11b+ myeloid cells in mdx muscles during the degenerative and regenerative stages of the pathology. CD11b+ myeloid cells were closely associated with the membrane of ICAM-1 myofibers and within necrotic myofibers. These observations may indicate that myofiber expression of ICAM-1 serves as a mechanism by which myeloid cells attach to skeletal muscle and exacerbate the myopathy in mdx mice.Next, the hypotheses that ICAM-1 expression was elevated after skeletal muscle injury and that its expression contributes to muscle regeneration were tested. EDL muscles of wild type and ICAM-1-/- mice were injected with cardiotoxin to induce muscle injury and markers of regeneration (percentage of regenerating myofibers, eMHC expression, and CSA of regenerating myofibers) were measured at 5, 7, 10, and 14 days of recovery. Western blot revealed elevated expression of ICAM-1 in wild type muscles after injury compared to control. ICAM-1 was expressed on the membrane of normal and regenerating myofibers and by CD11b+ myeloid cells in wild type muscles after injury. At 10 days after injury, CSA of regenerating myofibers was significantly elevated in wild type muscles compared to ICAM-1-/-, but similar between strains 14 days after injury. The percentage of regenerating myofibers and the expression of eMHC after injury were similar between wild type and ICAM-1-/- injured muscles. These findings indicate that the absence of ICAM-1 does not impair regeneration but may delay the growth of regenerating myofibers after injury. Overall, the novel findings in this study characterize the expression and localization of ICAM-1 in skeletal muscle disease and regeneration, and provide us with a greater insight on potential mechanisms by which its expression may contribute to muscle regeneration. 2016 English text University of Toledo / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=toledo1461860958 http://rave.ohiolink.edu/etdc/view?acc_num=toledo1461860958 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Physiology
Biology
Kinesiology
ICAM-1
skeletal muscle
regeneration
mdx
inflammatory response
adhesion molecule
muscle injury
spellingShingle Physiology
Biology
Kinesiology
ICAM-1
skeletal muscle
regeneration
mdx
inflammatory response
adhesion molecule
muscle injury
Torres-Palsa, Maria Jose
ICAM-1 in Skeletal Muscle Disease and Regeneration
author Torres-Palsa, Maria Jose
author_facet Torres-Palsa, Maria Jose
author_sort Torres-Palsa, Maria Jose
title ICAM-1 in Skeletal Muscle Disease and Regeneration
title_short ICAM-1 in Skeletal Muscle Disease and Regeneration
title_full ICAM-1 in Skeletal Muscle Disease and Regeneration
title_fullStr ICAM-1 in Skeletal Muscle Disease and Regeneration
title_full_unstemmed ICAM-1 in Skeletal Muscle Disease and Regeneration
title_sort icam-1 in skeletal muscle disease and regeneration
publisher University of Toledo / OhioLINK
publishDate 2016
url http://rave.ohiolink.edu/etdc/view?acc_num=toledo1461860958
work_keys_str_mv AT torrespalsamariajose icam1inskeletalmusclediseaseandregeneration
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