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. 2024 Apr 3;29(1):216.
doi: 10.1186/s40001-024-01812-9.

Desmin gene expression is not ubiquitous in all upper airway myofibers and the pattern differs between healthy and sleep apnea subjects

Per Stål  1 , Hanna Nord  1 , Jonas von Hofsten  1 , Thorbjörn Holmlund  2 , Farhan Shah  3
Affiliations

Desmin gene expression is not ubiquitous in all upper airway myofibers and the pattern differs between healthy and sleep apnea subjects

Per Stål et al. Eur J Med Res. .

Abstract

Background: Desmin is a major cytoskeletal protein considered ubiquitous in mature muscle fibers. However, we earlier reported that a subgroup of muscle fibers in the soft palate of healthy subjects and obstructive sleep apnea patients (OSA) lacked immunoexpression for desmin. This raised the question of whether these fibers also lack messenger ribonucleic acid (mRNA) for desmin and can be considered a novel fiber phenotype. Moreover, some fibers in the OSA patients had an abnormal distribution and aggregates of desmin. Thus, the aim of the study was to investigate if these desmin protein abnormalities are also reflected in the expression of desmin mRNA in an upper airway muscle of healthy subjects and OSA patients.

Methods: Muscle biopsies from the musculus uvulae in the soft palate were obtained from ten healthy male subjects and six male patients with OSA. Overnight sleep apnea registrations were done for all participants. Immunohistochemistry, in-situ hybridization, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) techniques were used to evaluate the presence of desmin protein and its mRNA.

Results: Our findings demonstrated that a group of muscle fibers lacked expression for desmin mRNA and desmin protein in healthy individuals and OSA patients (12.0 ± 5.6% vs. 23.1 ± 10.8%, p = 0.03). A subpopulation of these fibers displayed a weak subsarcolemmal rim of desmin accompanied by a few scattered mRNA dots in the cytoplasm. The muscles of OSA patients also differed from healthy subjects by exhibiting muscle fibers with reorganized or accumulated aggregates of desmin protein (14.5 ± 6.5%). In these abnormal fibers, the density of mRNA was generally low or concentrated in specific regions. The overall quantification of desmin mRNA by RT-qPCR was significantly upregulated in OSA patients compared to healthy subjects (p = 0.01).

Conclusions: Our study shows evidence that muscle fibers in the human soft palate lack both mRNA and protein for desmin. This indicates a novel cytoskeletal structure and challenges the ubiquity of desmin in muscle fibers. Moreover, the observation of reorganized or accumulated aggregates of desmin mRNA and desmin protein in OSA patients suggests a disturbance in the transcription and translation process in the fibers of the patients.

Keywords: Cytoskeleton; Desmin; Muscle fiber injury; Obstructive sleep apnea; Snoring; Vibration; mRNA.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Overview of muscle cross-sections from the musculus uvula stained for H&E in a healthy individual A and a patient B. Note the high fiber size variability and high amount of connective tissue in the patient muscle. Scale bar = 50μm
Fig. 2
Fig. 2
Cross- (A, B) and longitudinal sections (C–G) from the uvula muscle of healthy subjects (A) and an OSA patient immunostained for desmin (DES, green) and laminin (white, except E). Bar graphs show the percentage of desmin negative fibers (H) and disorganized fibers (I) in healthy subjects and patients (* p<0.05, ** p<0.01). Muscle fibers showing typical positive DES expression are marked 1, fibers lacking DES are marked 2, and fibers with weak DES staining are marked 3. In the OSA patient, muscle fibers with segmental lack of DES are marked 4 and fibers with disorganized DES are marked 5. Note the higher variability in fiber size, connective tissue content, and irregularity in the distribution of DES in fibers from the patient compared to the healthy subjects. Note also the lower capillarization in the sample from the patient. Scale bar panels A–C=50μm, panels D–G = 25μm
Fig. 3
Fig. 3
Cross-sections from the uvula muscle showing different regions in a healthy subject (columns 1 and 2) and an OSA patient (column 3) immunostained for desmin (DES, green, A–C) and a riboprobe against desmin mRNA (red, D–F). Merged staining for DES and desmin mRNA are shown in panels G–I. Muscle fibers displaying either low or high mRNA expression in DES positive fibers (DES pos) are marked 1 and 2, respectively. Fibers lacking desmin (DES neg) and its mRNA are marked 3. Bar graph (J) shows the percentage of DES neg fibers with absence or very low mRNA expression in healthy subjects and patients (p=0.05). Note the intra-myofibrillar maldistribution and accumulations of mRNA (arrows) as well as the higher number of fibers lacking expression for DES and its mRNA in OSA patients. Scale bar=50μm
Fig. 4
Fig. 4
Cross-sections from different areas of the uvula muscle of an OSA patient stained for desmin (DES, green), its corresponding mRNA (red), and DAPI (nuclei blue). Panel A show an area in the muscle with a relatively normal morphology, while panel B shows an area with an abnormal appearance. In panel B, note the high variability in fiber size and fiber form, the presence of fibrosis, the generally lower expression of mRNA, and the presence of fibers lacking immunostaining for both DES and its mRNA (asterisks). Scale bar=50μm. In panel C, the bar graph shows significantly higher expression values of desmin mRNA (*) in the OSA patients than in the healthy subjects, as revealed by RT-qPCR
Fig. 5
Fig. 5
Longitudinally sectioned muscle fibers from a patient showing the expression of desmin mRNA (A–C, red) and merged expression of desmin mRNA and desmin (DES) protein (red and green, respectively, D–F). A and D show a fiber with a presence of desmin mRNA in a typical striated pattern of DES. B and E show a fiber with a more irregular distribution of both mRNA and DES. C and F show a fiber with a segmental lack of immunoreaction for DES and its mRNA. Note that mRNA and the protein for desmin also are maldistributed and accumulated in these fibers (C and F). Scale bar = 25 µm
Fig. 6
Fig. 6
The figures illustrate the co-expression of desmin (DES, green) and desmin mRNA (red) in longitudinal (A, C, E) and cross-sectioned (B, D, E1 and E2) muscle fibers from an OSA patient. A and B show the expression pattern of DES and its mRNA in a normal fiber, and C and D show the expression pattern of mRNA in a fiber with disorganized DES. E reveals the staining pattern in a longitudinally sectioned fiber segmentally lacking DES and its mRNA. Note the accumulation of desmin mRNA in the area showing expression of DES (E and E1, marked a) and the lack of mRNA in the area lacking DES (E and E2, marked b). Scale bar = 25 µm
Fig. 7
Fig. 7
Muscle cross-sections from an OSA patient stained for desmin (DES, green, A, D, G), desmin mRNA (red, B, E, H), and merged staining with DAPI (nuclei blue) (C, F, I). A–C show a fiber with a region lacking DES but having a dense immunoreaction for its mRNA (arrows). D–F show a vacuole-like structure lacking immunostaining for DES and its mRNA (arrows). G–I show a circular area within the fiber having a very low expression of the DES but normal expression of desmin mRNA (arrows). Scale bar = 25 µm
Fig. 8
Fig. 8
Cross-sections of muscle fibers displaying an abnormal expression of desmin protein and corresponding mRNA in OSA patients (A–I). The sections are stained for the desmin protein (DES, green), desmin mRNA (red), and DAPI (nuclei blue). Panel A shows a fiber with disorganized DES, very low expression of desmin mRNA, and an internal nuclei (arrow). Ringed fibers showing different patterns of maldistributed DES and corresponding mRNA are shown in panels B and C. Panel D shows a fiber with very weak staining for DES and a focal subsarcolemmal area filled with desmin mRNA (arrow). Panels E and F show a slender fiber-like structure (arrows) in close connection with a large fiber lacking or having a low amount of DES (asterisks). Note the very low expression of desmin mRNA in the slender fiber in panel E and very dense expression in the fiber in panel F. Panels G and H shows split fibers (arrows) almost entirely lacking both DES and its mRNA. Note in panel H that the fiber has an extension filled with desmin mRNA (arrowhead). Panel I show a fiber having a large extension lacking DES with a small subsarcolemmal accumulation of desmin mRNA (arrow). Scale bar=25μm
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