Inducible Heat Shock Protein 70 Levels in Patients and the mdx Mouse Affirm Regulation during Skeletal Muscle Regeneration in Muscular Dystrophy
Background: Stress-inducible heat shock protein 70 (HSP70) is both a protective chaperone involved in protein homeostasis and an immune regulator. In both capacities, HSP70 has been implicated in muscle disorders, yet with fragmented and differing results. In this study we aimed to compare results o...
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| Format: | Article |
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IMR Press
2022-07-01
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| Series: | Frontiers in Bioscience-Scholar |
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| Online Access: | https://www.imrpress.com/journal/FBS/14/3/10.31083/j.fbs1403019 |
| _version_ | 1798000469917827072 |
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| author | Gwenny Cosemans Caroline Merckx Jan L. De Bleecker Boel De Paepe |
| author_facet | Gwenny Cosemans Caroline Merckx Jan L. De Bleecker Boel De Paepe |
| author_sort | Gwenny Cosemans |
| collection | DOAJ |
| description | Background: Stress-inducible heat shock protein 70 (HSP70) is both a protective chaperone involved in protein homeostasis and an immune regulator. In both capacities, HSP70 has been implicated in muscle disorders, yet with fragmented and differing results. In this study we aimed to compare results obtained in the mouse model for the severest form of muscular dystrophy (MD) equivalent to Duchenne MD, termed the mdx mouse, with results obtained in human MD. Methods: Skeletal muscle and serum samples were obtained from 11 healthy controls, 11 fully characterized patients diagnosed with Becker MD and limb girdle MD (LGMD), and six muscle disease controls. In addition, muscle extracts were prepared from tibialis anterior of mdx and control mice at ages 4, 8 and 12 weeks. The HSP70 levels were quantified using RT-PCR, western blotting and protein arrays, and localized in muscle tissue sections using double immunofluorescence. Results: We found selective and significant 2.2-fold upregulation of HSP70 protein in mdx tibialis muscle at the earliest disease phase only. In LGMD and Becker MD patients, HSP70 protein levels were not significantly different from those of healthy muscle and serum. HSP70 was localized to regenerating muscle fibers both in mouse and human MD skeletal muscle tissues. Toll-like receptor (TLR) 2 and TLR4 expression was moderately increased on the sarcolemma in MD muscle, yet protein levels were not significantly different from normal controls. Conclusions: HSP70 upregulation in MD appears disease stage-dependent, marking the phase of most active muscle regeneration in the mdx mouse. We postulate that well-timed supportive therapeutic interventions with HSP70 agonists could potentially improve muscle tissue’s regenerative capacities in MD, attenuating loss of muscle mass while we await gene therapies to become more widely available. |
| first_indexed | 2024-04-11T11:20:47Z |
| format | Article |
| id | doaj.art-9cf176aff49f4e6486a06ab3770f8b63 |
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| language | English |
| last_indexed | 2024-04-11T11:20:47Z |
| publishDate | 2022-07-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Scholar |
| spelling | doaj.art-9cf176aff49f4e6486a06ab3770f8b632022-12-22T04:27:04ZengIMR PressFrontiers in Bioscience-Scholar1945-05162022-07-011431910.31083/j.fbs1403019S1945-0516(22)00064-8Inducible Heat Shock Protein 70 Levels in Patients and the mdx Mouse Affirm Regulation during Skeletal Muscle Regeneration in Muscular DystrophyGwenny Cosemans0Caroline Merckx1Jan L. De Bleecker2Boel De Paepe3Laboratory for Neuropathology, Department of Neurology, Ghent University, 9000 Ghent, BelgiumLaboratory for Neuropathology, Department of Neurology, Ghent University, 9000 Ghent, BelgiumLaboratory for Neuropathology, Department of Neurology, Ghent University, 9000 Ghent, BelgiumLaboratory for Neuropathology, Department of Neurology, Ghent University, 9000 Ghent, BelgiumBackground: Stress-inducible heat shock protein 70 (HSP70) is both a protective chaperone involved in protein homeostasis and an immune regulator. In both capacities, HSP70 has been implicated in muscle disorders, yet with fragmented and differing results. In this study we aimed to compare results obtained in the mouse model for the severest form of muscular dystrophy (MD) equivalent to Duchenne MD, termed the mdx mouse, with results obtained in human MD. Methods: Skeletal muscle and serum samples were obtained from 11 healthy controls, 11 fully characterized patients diagnosed with Becker MD and limb girdle MD (LGMD), and six muscle disease controls. In addition, muscle extracts were prepared from tibialis anterior of mdx and control mice at ages 4, 8 and 12 weeks. The HSP70 levels were quantified using RT-PCR, western blotting and protein arrays, and localized in muscle tissue sections using double immunofluorescence. Results: We found selective and significant 2.2-fold upregulation of HSP70 protein in mdx tibialis muscle at the earliest disease phase only. In LGMD and Becker MD patients, HSP70 protein levels were not significantly different from those of healthy muscle and serum. HSP70 was localized to regenerating muscle fibers both in mouse and human MD skeletal muscle tissues. Toll-like receptor (TLR) 2 and TLR4 expression was moderately increased on the sarcolemma in MD muscle, yet protein levels were not significantly different from normal controls. Conclusions: HSP70 upregulation in MD appears disease stage-dependent, marking the phase of most active muscle regeneration in the mdx mouse. We postulate that well-timed supportive therapeutic interventions with HSP70 agonists could potentially improve muscle tissue’s regenerative capacities in MD, attenuating loss of muscle mass while we await gene therapies to become more widely available.https://www.imrpress.com/journal/FBS/14/3/10.31083/j.fbs1403019becker muscular dystrophyduchenne muscular dystrophyheat shock protein 70limb girdle muscular dystrophymuscle regeneration |
| spellingShingle | Gwenny Cosemans Caroline Merckx Jan L. De Bleecker Boel De Paepe Inducible Heat Shock Protein 70 Levels in Patients and the mdx Mouse Affirm Regulation during Skeletal Muscle Regeneration in Muscular Dystrophy Frontiers in Bioscience-Scholar becker muscular dystrophy duchenne muscular dystrophy heat shock protein 70 limb girdle muscular dystrophy muscle regeneration |
| title | Inducible Heat Shock Protein 70 Levels in Patients and the mdx Mouse Affirm Regulation during Skeletal Muscle Regeneration in Muscular Dystrophy |
| title_full | Inducible Heat Shock Protein 70 Levels in Patients and the mdx Mouse Affirm Regulation during Skeletal Muscle Regeneration in Muscular Dystrophy |
| title_fullStr | Inducible Heat Shock Protein 70 Levels in Patients and the mdx Mouse Affirm Regulation during Skeletal Muscle Regeneration in Muscular Dystrophy |
| title_full_unstemmed | Inducible Heat Shock Protein 70 Levels in Patients and the mdx Mouse Affirm Regulation during Skeletal Muscle Regeneration in Muscular Dystrophy |
| title_short | Inducible Heat Shock Protein 70 Levels in Patients and the mdx Mouse Affirm Regulation during Skeletal Muscle Regeneration in Muscular Dystrophy |
| title_sort | inducible heat shock protein 70 levels in patients and the mdx mouse affirm regulation during skeletal muscle regeneration in muscular dystrophy |
| topic | becker muscular dystrophy duchenne muscular dystrophy heat shock protein 70 limb girdle muscular dystrophy muscle regeneration |
| url | https://www.imrpress.com/journal/FBS/14/3/10.31083/j.fbs1403019 |
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