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Stål, Per
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Tran, P., Wanrooij, P. H., Lorenzon, P., Sharma, S., Thelander, L., Nilsson, A. K., . . . Chabes, A. (2019). De novo dNTP production is essential for normal postnatal murine heart development. Journal of Biological Chemistry, Article ID jbc.RA119.009492.
Open this publication in new window or tab >>De novo dNTP production is essential for normal postnatal murine heart development
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2019 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, article id jbc.RA119.009492Article in journal (Refereed) Epub ahead of print
Abstract [en]

The building blocks of DNA, dNTPs, can be produced de novo or can be salvaged from deoxyribonucleosides. However, to what extent the absence of de novo dNTP production can be compensated for by the salvage pathway is unknown. Here, we eliminated de novo dNTP synthesis in the mouse heart and skeletal muscle by inactivating ribonucleotide reductase (RNR), a key enzyme for the de novo production of dNTPs, at embryonic day 13. All other tissues had normal de novo dNTP synthesis and theoretically could supply heart and skeletal muscle with deoxyribonucleosides needed for dNTP production by salvage. We observed that the dNTP and NTP pools in wild-type postnatal hearts are unexpectedly asymmetric, with unusually high dGTP and GTP levels compared with those in whole mouse embryos or murine cell cultures. We found that RNR inactivation in heart led to strongly decreased dGTP and increased dCTP, dTTP, and dATP pools; aberrant DNA replication; defective expression of muscle-specific proteins; progressive heart abnormalities; disturbance of the cardiac conduction system; and lethality between the second and fourth weeks after birth. We conclude that dNTP salvage cannot substitute for de novo dNTP synthesis in the heart and that cardiomyocytes and myocytes initiate DNA replication despite an inadequate dNTP supply. We discuss the possible reasons for the observed asymmetry in dNTP and NTP pools in wildtype hearts.

Keywords
cardiac function, cardiac muscle, dNTP metabolism, dNTP salvage, deoxyribonucleoside kinases, desmin, heart development, nucleoside/nucleotide biosynthesis, nucleoside/nucleotide metabolism, ribonucleotide reductase
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-161767 (URN)10.1074/jbc.RA119.009492 (DOI)31300555 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer Society
Available from: 2019-07-30 Created: 2019-07-30 Last updated: 2019-08-06
Shah, F., Franklin, K. A., Holmlund, T., Levring Jäghagen, E., Berggren, D., Forsgren, S. & Stål, P. (2019). Desmin and dystrophin abnormalities in upper airway muscles of snorers and patients with sleep apnea. Respiratory Research, 20, Article ID 31.
Open this publication in new window or tab >>Desmin and dystrophin abnormalities in upper airway muscles of snorers and patients with sleep apnea
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2019 (English)In: Respiratory Research, ISSN 1465-993X, Vol. 20, article id 31Article in journal (Refereed) Published
Abstract [en]

The pathophysiology of obstruction and swallowing dysfunction in snores and sleep apnea patients remains unclear. Neuropathy and to some extent myopathy have been suggested as contributing causes. Recently we reported an absence and an abnormal isoform of two cytoskeletal proteins, desmin, and dystrophin, in upper airway muscles of healthy humans. These cytoskeletal proteins are considered vital for muscle function. We aimed to investigate for muscle cytoskeletal abnormalities in upper airways and its association with swallowing dysfunction and severity of sleep apnea. Cytoskeletal proteins desmin and dystrophin were morphologically evaluated in the uvula muscle of 22 patients undergoing soft palate surgery due to snoring and sleep apnea and in 10 healthy controls. The muscles were analysed with immunohistochemical methods, and swallowing function was assessed using videoradiography. Desmin displayed a disorganized pattern in 21 +/- 13% of the muscle fibres in patients, while these fibers were not present in controls. Muscle fibres lacking desmin were present in both patients and controls, but the proportion was higher in patients (25 +/- 12% vs. 14 +/- 7%, p = 0.009). The overall desmin abnormalities were significantly more frequent in patients than in controls (46 +/- 18% vs. 14 +/- 7%, p < 0.001). In patients, the C-terminus of the dystrophin molecule was absent in 19 +/- 18% of the desmin-abnormal muscle fibres. Patients with swallowing dysfunction had 55 +/- 10% desmin-abnormal muscle fibres vs. 22 +/- 6% in patients without swallowing dysfunction, p = 0.002. Cytoskeletal abnormalities in soft palate muscles most likely contribute to pharyngeal dysfunction in snorers and sleep apnea patients. Plausible causes for the presence of these abnormalities is traumatic snoring vibrations, tissue stretch or muscle overload.

Place, publisher, year, edition, pages
BioMed Central, 2019
Keywords
Muscle, Upper airway dysfunction, Dysphagia, Pathophysiology, Cytoskeletal abnormalities, desmin, dystrophin
National Category
Cell and Molecular Biology Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-157211 (URN)10.1186/s12931-019-0999-9 (DOI)000459188400003 ()30764835 (PubMedID)
Available from: 2019-04-08 Created: 2019-04-08 Last updated: 2019-04-08Bibliographically approved
Frykholm, E., Klijn, P., Saey, D., van Hees, H. W. H., Stål, P., Sandström, T., . . . Nyberg, A. (2019). Effect and feasibility of non-linear periodized resistance training in people with COPD: study protocol for a randomized controlled trial. Trials, 20(1), Article ID 6.
Open this publication in new window or tab >>Effect and feasibility of non-linear periodized resistance training in people with COPD: study protocol for a randomized controlled trial
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2019 (English)In: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 20, no 1, article id 6Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: In people with chronic obstructive pulmonary disease (COPD), limb-muscle dysfunction is one of the most troublesome systemic manifestations of the disease, which at the functional level is evidenced by reduced strength and endurance of limb muscles. Improving limb-muscle function is an important therapeutic goal of COPD management, for which resistance training is recommended. However, current guidelines for resistance training in COPD mainly focus on improving muscle strength which only reflects one aspect of limb-muscle function and does not address the issue of reduced muscle endurance. The latter is of importance considering that the reduction in limb-muscle endurance often is greater than that of muscle weakness, and also, limb-muscle endurance seems to be closer related to walking capacity as well as arm function than to limb-muscle strength within this group of people. Thus, strategies targeting multiple aspects of the decreased muscle function are warranted to increase the possibility for an optimal effect for the individual patient. Periodized resistance training, which represents a planned variation of resistance training variables (i.e., volume, intensity, frequency, etc.), is one strategy that could be used to target limb-muscle strength as well as limb-muscle endurance within the same exercise regimen.

METHODS: This is an international, multicenter, randomized controlled trial comparing the effect and feasibility of non-linear periodized resistance training to traditional non-periodized resistance training in people with COPD. Primary outcomes are dynamic limb-muscle strength and endurance. Secondary outcomes include static limb-muscle strength and endurance, functional performance, quality of life, dyspnea, intramuscular adaptations as well as the proportion of responders. Feasibility of the training programs will be assessed and compared on attendance rate, duration, satisfaction, drop-outs as well as occurrence and severity of any adverse events.

DISCUSSION: The proposed trial will provide new knowledge to this research area by investigating and comparing the feasibility and effects of non-linear periodized resistance training compared to traditional non-periodized resistance training. If the former strategy produces larger physiological adaptations than non-periodized resistance training, this project may influence the prescription of resistance training in people with COPD.

TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03518723 . Registered on 13 April 2018.

Place, publisher, year, edition, pages
BioMed Central, 2019
Keywords
Functional performance, Limb-muscle endurance, Limb-muscle strength, Pulmonary disease, chronic obstructive
National Category
Physiotherapy
Research subject
physiotherapy
Identifiers
urn:nbn:se:umu:diva-154980 (URN)10.1186/s13063-018-3129-y (DOI)000454906600006 ()30606240 (PubMedID)
Funder
Swedish Research Council, 2016-01802Swedish Heart Lung Foundation, E 127/16
Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-01-25Bibliographically approved
Shah, F., Forsgren, S., Holmlund, T., Jaghagen, E. L., Berggren, D., Franklin, K. A. & Stål, P. (2019). Neurotrophic factor BDNF is upregulated in soft palate muscles of snorers and sleep apnea patients. Laryngoscope Investigative Otolaryngology, 4(1), 174-180
Open this publication in new window or tab >>Neurotrophic factor BDNF is upregulated in soft palate muscles of snorers and sleep apnea patients
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2019 (English)In: Laryngoscope Investigative Otolaryngology, ISSN 2378-8038, Vol. 4, no 1, p. 174-180Article in journal (Refereed) Published
Abstract [en]

Objectives: Neuromuscular injuries are suggested to contribute to upper airway collapse and swallowing dysfunction in patients with sleep apnea. Neurotrophins, a family of proteins involved in survival, development, and function of neurons, are reported to be upregulated in limb muscle fibers in response to overload and nerve damage. We aimed to investigate the expression of two important neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), in muscle fibers of uvula from snorers and sleep apnea patients and to compare these findings with pharyngeal function.

Methods: Uvula muscle biopsies from 22 patients and 10 controls were analyzed for BDNF, NGF, and cytoskeletal protein desmin using immunohistochemistry. Pharyngeal swallowing function was assessed using videoradiography.

Results: BDNF, but not NGF, was significantly upregulated in a subpopulation of muscle fibers in snoring and sleep apnea patients. Two major immunoreaction patterns for BDNF were observed; a fine grainy point like BDNF staining was displayed in muscle fibers of both patients and controls (41 +/- 23 vs. 25 +/- 17%, respectively, P = .06), while an abnormal upregulated intense-dotted or disorganized reaction was mainly observed in patients (8 +/- 8 vs. 2 +/- 2%, P = .02). The latter fibers, which often displayed an abnormal immunoreaction for desmin, were more frequent in patients with than without swallowing dysfunction (10 +/- 8 vs. 3 +/- 3%, P = .05).

Conclusion: BDNF is upregulated in the upper airway muscles of snorers and sleep apnea patients, and especially in patients with swallowing dysfunction. Upregulation of BDNF is suggested to be a response to denervation, reinnervation, and repair of injured muscle fibers. Our findings propose that damaged upper airway muscles might heal following treatment for snoring and sleep apnea.

Place, publisher, year, edition, pages
Wiley Periodicals, Inc., 2019
Keywords
Neurotrophins, brain-derived neurotrophic factor (BDNF), nerve-derived neurotrophic factor GF), snorers, obstructive sleep apnea, OSA, swallowing dysfunction, desmin, neuromuscular injury, nerve, muscle fiber
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-157217 (URN)10.1002/lio2.225 (DOI)000459339700027 ()30828636 (PubMedID)
Available from: 2019-03-25 Created: 2019-03-25 Last updated: 2019-03-25Bibliographically approved
Shah, F., Stål, P., Li, J., Sessle, B. J. & Avivi-Arber, L. (2019). Tooth extraction and subsequent dental implant placement in Sprague-Dawley rats induce differential changes in anterior digastric myofibre size and myosin heavy chain isoform expression. Archives of Oral Biology, 99, 141-149
Open this publication in new window or tab >>Tooth extraction and subsequent dental implant placement in Sprague-Dawley rats induce differential changes in anterior digastric myofibre size and myosin heavy chain isoform expression
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2019 (English)In: Archives of Oral Biology, ISSN 0003-9969, E-ISSN 1879-1506, Vol. 99, p. 141-149Article in journal (Refereed) Published
Abstract [en]

Objective: to determine if tooth loss and dental implant placement in rats induce changes in the morphological and histochemical features of the Anterior Digastric muscle.

Design: Adult male Sprague-Dawley rats had their right maxillary molar teeth extracted. ‘Extraction-1’ and ‘Extraction-2 groups were sacrificed, respectively, 4 or 8 weeks later, and an Implant group had an implant placement 2 weeks after the molar extraction, and rats were sacrificed 3 weeks later (n = 4/group). Naive rats (n = 3) had no treatment. Morphometric and immunohistochemical techniques quantified Anterior Digastric muscle myofibres’ cross-sectional area (CSA) and myosin heavy chain (MyHC) isoform proportions. Significant ANOVAs were followed by post-hoc tests; p < 0.05 and 0.1 were considered to reflect levels of statistical significance.

Results: In naïve rats, the peripheral regions of the Anterior Digastric muscle was dominated by MyHC-IIx/b isoform and there were no MyHC-I isoforms; the central regions dominated by MyHC-IIx/b and MyHC-IIa isoforms. Compared with naive rats, tooth extraction produced, 8 (but not 4) weeks later, a decreased proportion of fast-contracting fatigue-resistant MyHC-IIa isoform (p = 0.08), and increased proportion of fast and intermediate fatigue-resistance MyHC-IIa/x/b isoform (p = 0.03). Dental implant placement following tooth extraction attenuated the extraction effects but produced a decreased proportion of fast-contracting fatiguable MyHC-llx/b isoform (p = 0.03) in the peripheral region, and increased inter-animal variability in myofibre-CSAs.

Conclusions: Given the crucial role that the Anterior Digastric muscle plays in many vital oral functions (e.g., chewing, swallowing), these changes may contribute to the changes in oral sensorimotor functions that occur in humans following such treatments.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Anterior digastric, Jaw-opening muscle, Masticatory muscle, Myosin heavy chain, Myofibre-type, Heterogeneity
National Category
Dentistry
Identifiers
urn:nbn:se:umu:diva-157771 (URN)10.1016/j.archoralbio.2019.01.009 (DOI)000460850900018 ()30684691 (PubMedID)2-s2.0-85060298074 (Scopus ID)
Available from: 2019-04-03 Created: 2019-04-03 Last updated: 2019-04-03Bibliographically approved
Shah, F., Holmlund, T., Levring Jäghagen, E., Berggren, D., Franklin, K. A., Forsgren, S. & Stål, P. (2018). Axon and Schwann Cell Degeneration in Nerves of Upper Airway Relates to Pharyngeal Dysfunction in Snorers and Patients With Sleep Apnea. Chest, 154(5), 1091-1098
Open this publication in new window or tab >>Axon and Schwann Cell Degeneration in Nerves of Upper Airway Relates to Pharyngeal Dysfunction in Snorers and Patients With Sleep Apnea
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2018 (English)In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 154, no 5, p. 1091-1098Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The pathophysiologic mechanism of nocturnal obstruction and swallowing dysfunction commonly occurring in patients with sleep apnea is unclear. The goal of this study was to investigate whether nerve injuries in the upper airways of snorers and patients with sleep apnea are associated with pharyngeal dysfunction and severity of sleep apnea.

METHODS: Twenty-two patients undergoing palatal surgery due to snoring and sleep apnea were investigated for a swallowing dysfunction by using videoradiography. Twelve healthy nonsnoring subjects were included as control subjects. Tissue samples from the soft palate at the base of the uvula were obtained in all patients and control subjects. Nerves and muscle were analyzed with immunohistochemical and morphologic methods, and the findings were correlated with swallowing function and degree of sleep apnea.

RESULTS: In the soft palate of patients, nerve fascicles exhibited a significantly lower density of axons (5.4 vs 17.9 x 10(-3) axons/mu m(2); P = .02), a smaller percentage area occupied by Schwann cells (17.5% vs 45.2%; P = .001) and a larger number of circular shaped Schwann cells lacking central axons (43.0% vs 12.7%; P < 0.001) compared with control subjects. The low density of axons was significantly related to degree of swallowing dysfunction (r = 0.5; P = .03) and apnea-hypopnea index > 5 (P = .03). Regenerating axons were frequently observed in patients compared with control subjects (11.3 +/- 4.2% vs 4.8 +/- 2.4%; P = .02).

CONCLUSIONS: Axon degeneration in preterminal nerves of the soft palate is associated with pharyngeal dysfunction in snorers and patients with sleep apnea. The most likely cause for the nerve injuries is traumatic snoring vibrations and tissue stretch, leading to swallowing dysfunction and increased risk for upper airway obstruction during sleep.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
muscle degeneration, nerve injury, OSA, swallowing dysfunction, upper airways
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-153546 (URN)10.1016/j.chest.2018.06.017 (DOI)000449273000023 ()29966666 (PubMedID)
Funder
Swedish Heart Lung Foundation, 20110210Swedish Heart Lung Foundation, 20140339
Available from: 2018-11-22 Created: 2018-11-22 Last updated: 2018-11-22Bibliographically approved
Edmundsson, D. S., Toolanen, G. L. & Stål, P. S. (2018). Muscle changes in patients with diabetes and chronic exertional compartment syndrome before and after treatment with fasciotomy. Muscle and Nerve, 57(2), 229-239
Open this publication in new window or tab >>Muscle changes in patients with diabetes and chronic exertional compartment syndrome before and after treatment with fasciotomy
2018 (English)In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 57, no 2, p. 229-239Article in journal (Refereed) Published
Abstract [en]

Introduction: Muscle changes in patients with diabetes and lower leg pain due to chronic exertional compartment syndrome (CECS) were investigated before and after fasciotomy. Methods: The tibialis anterior muscle was analyzed with histochemical and morphological techniques in 7 patients with diabetes and CECS before fasciotomy and in 5 of them 1 year after fasciotomy. Nondiabetic patients with CECS and healthy participants served as references. Results: Before treatment, walking distance until occurrence of pain was limited (<0.2 km). Intramuscular pressure was significantly higher than in reference participants. Muscle analysis showed changes pathognomonic for neuropathy and myopathy and a restricted capillary network, with significantly more severe changes in the muscles of patients with diabetes than in the muscles of nondiabetic patients. Treatment with fasciotomy improved clinical signs, increased walking ability, and reduced muscle abnormalities, but muscle capillarization remained low. Discussion: Patients with diabetes and CECS have distinct pathological changes in affected muscles. Pressure-relieving fasciotomy triggers a regenerative response in the muscle tissue but not in the capillary bed.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
angiopathy, capillaries, compartment syndrome, diabetes, fasciotomy, muscle, myopathy, uropathy
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-144342 (URN)10.1002/mus.25715 (DOI)000419964700016 ()28561900 (PubMedID)
Available from: 2018-02-07 Created: 2018-02-07 Last updated: 2019-05-17Bibliographically approved
Von Walden, F., Gantelius, S., Liu, C., Borgström, H., Björk, L., Gremark, O., . . . Ponten, E. (2018). Muscle contractures in patients with cerebral palsy and acquired brain injury are associated with extracellular matrix expansion, pro-inflammatory gene expression, and reduced rRNA synthesis. Muscle and Nerve, 58(2), 277-285
Open this publication in new window or tab >>Muscle contractures in patients with cerebral palsy and acquired brain injury are associated with extracellular matrix expansion, pro-inflammatory gene expression, and reduced rRNA synthesis
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2018 (English)In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 58, no 2, p. 277-285Article in journal (Refereed) Published
Abstract [en]

Introduction: Children with cerebral palsy (CP) and acquired brain injury (ABI) commonly develop muscle contractures with advancing age. An underlying growth defect contributing to skeletal muscle contracture formation in CP/ABI has been suggested.

Methods: The biceps muscles of children and adolescents with CP/ABI (n=20) and typically developing controls (n=10) were investigated. We used immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blotting to assess gene expression relevant to growth and size homeostasis.

Results: Classical pro-inflammatory cytokines and genes involved in extracellular matrix (ECM) production were elevated in skeletal muscle of children with CP/ABI. Intramuscular collagen content was increased and satellite cell number decreased and this was associated with reduced levels of RNA polymerase I transcription factors, 45s pre-rRNA and 28S rRNA.

Discussion: The present study provides novel data suggesting a role for pro-inflammatory cytokines and reduced ribosomal production in the development/maintenance of muscle contractures, possibly underlying stunted growth and perimysial ECM expansion.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2018
Keywords
cerebral palsy, cytokine, extracellular matrix, ribosome biogenesis, skeletal muscle
National Category
Physiology
Identifiers
urn:nbn:se:umu:diva-152418 (URN)10.1002/mus.26130 (DOI)000445090300023 ()29572878 (PubMedID)
Funder
Stockholm County Council
Available from: 2018-10-05 Created: 2018-10-05 Last updated: 2018-10-05Bibliographically approved
Renström, L., Stål, P., Song, Y. & Forsgren, S. (2017). Bilateral muscle fiber and nerve influences by TNF-alpha in response to unilateral muscle overuse: studies on TNF receptor expressions. BMC Musculoskeletal Disorders, 18(1), Article ID 498.
Open this publication in new window or tab >>Bilateral muscle fiber and nerve influences by TNF-alpha in response to unilateral muscle overuse: studies on TNF receptor expressions
2017 (English)In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 18, no 1, article id 498Article in journal (Other academic) Published
Abstract [en]

Background:

TNF-alpha is suggested to be involved in muscle damage and muscle inflammation (myositis). In order to evaluate whether TNF-alpha is involved in the myositis that occurs in response to muscle overuse, the aim was to examine the expression patterns of TNF receptors in this condition.

Methods:

A rabbit muscle overuse model leading to myositis in the soleus muscle was used. The expression patterns of the two TNF receptors Tumor Necrosis Factor Receptor type 1 (TNFR1) and Tumor Necrosis Factor Receptor type 2 (TNFR2) were investigated. In situ hybridization and immunofluorescence were utilized. Immunostainings for desmin, NK-1R and CD31 were made in parallel.

Results:

Immunoreactions (IR) for TNF receptors were clearly observed in white blood cells, fibroblasts and vessel walls, and most interestingly also in muscle fibers and nerve fascicles in the myositis muscles. There were very restricted reactions for these in the muscles of controls. The upregulation of TNF receptors was for all types of structures seen for both the experimental side and the contralateral nonexperimental side. TNF receptor expressing muscle fibers were present in myositis muscles. They can be related to attempts for reparation/regeneration, as evidenced from results of parallel stainings. Necrotic muscle fibers displayed TNFR1 mRNA and TNFR2 immunoreaction (IR) in the invading white blood cells. In myositis muscles, TNFR1 IR was observed in both axons and Schwann cells while TNFR2 IR was observed in Schwann cells. Such observations were very rarely made for control animals.

Conclusions:

The findings suggest that there is a pronounced involvement of TNF-alpha in the developing myositis process. Attempts for reparation of the muscle tissue seem to occur via both TNFR1 and TNFR2. As the myositis process also occurs in the nonexperimental side and as TNF receptors are confined to nerve fascicles bilaterally it can be asked whether TNF-alpha is involved in the spreading of the myositis process to the contralateral side via the nervous system. Taken together, the study shows that TNF-alpha is not only associated with the inflammation process but that both the muscular and nervous systems are affected and that this occurs both on experimental and nonexperimental sides.

Keywords
TNF-alpha, Myositis, Muscle, TNFR1, TNFR2, nerve structures
National Category
Basic Medicine
Identifiers
urn:nbn:se:umu:diva-141941 (URN)10.1186/s12891-017-1796-6 (DOI)000416424300005 ()29183282 (PubMedID)
Available from: 2017-11-15 Created: 2017-11-15 Last updated: 2018-06-09Bibliographically approved
Shah, F., Berggren, D., Holmlund, T., Levring Jäghagen, E. & Stål, P. (2016). Unique expression of cytoskeletal proteins in human soft palate muscles. Journal of Anatomy, 228(3), 487-494
Open this publication in new window or tab >>Unique expression of cytoskeletal proteins in human soft palate muscles
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2016 (English)In: Journal of Anatomy, ISSN 0021-8782, E-ISSN 1469-7580, Vol. 228, no 3, p. 487-494Article in journal (Refereed) Published
Abstract [en]

The human oropharyngeal muscles have a unique anatomy with diverse and intricate functions. To investigate if this specialization is also reflected in the cytoarchitecture of muscle fibers, intermediate filament proteins and the dystrophin-associated protein complex have been analyzed in two human palate muscles, musculus uvula (UV) and musculus palatopharyngeus (PP), with immunohistochenmical and morphological techniques. Human limb muscles were used as reference. The findings show that the soft palate muscle fibers have a cytoskeletal architecture that differs from the limb muscles. While all limb muscles showed immunoreaction for a panel of antibodies directed against different domains of cytoskeletal proteins desmin and dystrophin, a subpopulation of palate muscle fibers lacked or had a faint immunoreaction for desmin (UV 11.7% and PP 9.8%) and the C-terminal of the dystrophin molecule (UV 4.2% and PP 6.4%). The vast majority of these fibers expressed slow contractile protein myosin heavy chain I. Furthermore, an unusual staining pattern was also observed in these fibers for β-dystroglycan, caveolin-3 and neuronal nitric oxide synthase nNOS, which are all membrane-linking proteins associated with the dystrophin C-terminus. While the immunoreaction for nNOS was generally weak or absent, β-dystroglycan and caveolin-3 showed a stronger immunostaining. The absence or a low expression of cytoskeletal proteins otherwise considered ubiquitous and important for integration and contraction of muscle cells indicate a unique cytoarchitecture designed to meet the intricate demands of the upper airway muscles. It can be concluded that a subgroup of muscle fibers in the human soft palate appears to have special biomechanical properties, and their unique cytoarchitecture must be taken into account while assessing function and pathology in oropharyngeal muscles.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
Keywords
cytoskeleton, desmin, dystrophin, muscle fiber, palatopharyngeus, sleep apnea, soft palate, uvula
National Category
Otorhinolaryngology Physiology
Research subject
Human Anatomy
Identifiers
urn:nbn:se:umu:diva-115780 (URN)10.1111/joa.12417 (DOI)000373121100011 ()26597319 (PubMedID)
Funder
Swedish Heart Lung Foundation
Available from: 2016-02-04 Created: 2016-02-04 Last updated: 2018-06-07Bibliographically approved
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