Spatial proteomics of skeletal muscle using thin cryosections reveals metabolic adaptation at the muscle-tendon transition zone

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  • Luisa Schmidt
  • Michael Saynisch
  • Christian Hoegsbjerg
  • Andreas Schmidt
  • Mackey, Abigail
  • Jan Wilm Lackmann
  • Stefan Müller
  • Manuel Koch
  • Bent Brachvogel
  • Kjær, Michael
  • Philipp Antczak
  • Marcus Krüger
Morphological studies of skeletal muscle tissue provide insights into the architecture of muscle fibers, the surrounding cells, and the extracellular matrix (ECM). However, a spatial proteomics analysis of the skeletal muscle including the muscle-tendon transition zone is lacking. Here, we prepare cryotome muscle sections of the mouse soleus muscle and measure each slice using short liquid chromatography-mass spectrometry (LC-MS) gradients. We generate 3,000 high-resolution protein profiles that serve as the basis for a network analysis to reveal the complex architecture of the muscle-tendon junction. Among the protein profiles that increase from muscle to tendon, we find proteins related to neuronal activity, fatty acid biosynthesis, and the renin-angiotensin system (RAS). Blocking the RAS in cultured mouse tenocytes using losartan reduces the ECM synthesis. Overall, our analysis of thin cryotome sections provides a spatial proteome of skeletal muscle and reveals that the RAS acts as an additional regulator of the matrix within muscle-tendon junctions.
OriginalsprogEngelsk
Artikelnummer114374
TidsskriftCell Reports
Vol/bind43
Udgave nummer7
Antal sider22
ISSN2211-1247
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
We thank Gil Oreff and Florien Jenner (University of Veterinary Medicine Vienna) for providing the tenocyte cell line. This work was supported by the Cologne Cluster of Excellence on Cellular Stress Responses in Aging-associated Diseases (CECAD) EXC 299/2 ; the RELOC graduate school GRK 2550 ( DFG 411422114 ) and FOR2722/2 ( Kr\u00FCger_384170921/TP4, KR 3788/8-2 ; BB_FOR2722-407146744/TP1 (BR2304/12-1) , 270922282 (BR2309/9-2), and Koch_407164333/TP4 (KO2247/8-1). In addition, this work was supported by a major invest grant from the Deutsche Forschungsgemeinschaft ( INST 216/1163-1 FUGG and INST 216/1020-1 FUGG ) and the JPND2019-466-146 grant.

Funding Information:
We thank Gil Oreff and Florien Jenner (University of Veterinary Medicine Vienna) for providing the tenocyte cell line. This work was supported by the Cologne Cluster of Excellence on Cellular Stress Responses in Aging-associated Diseases (CECAD) EXC 299/2; the RELOC graduate school GRK 2550 (DFG 411422114) and FOR2722/2 (Kr\u00FCger_384170921/TP4, KR 3788/8-2; BB_FOR2722-407146744/TP1 (BR2304/12-1), 270922282 (BR2309/9-2), and Koch_407164333/TP4 (KO2247/8-1). In addition, this work was supported by a major invest grant from the Deutsche Forschungsgemeinschaft (INST 216/1163-1 FUGG and INST 216/1020-1 FUGG) and the JPND2019-466-146 grant. Conceptualization, L.S. and M. Kr\u00FCger; methodology, L.S. and M. Kr\u00FCger; software, L.S. and P.A.; validation, L.S. M.S. and C.H.; formal analysis, L.S. and P.A.; investigation, L.S.; resources, M. Kr\u00FCger, M. Kjaer, A.M. J.-W.L. A.S. S.M. B.B. and M. Koch; writing \u2013 original draft, L.S. M. Kr\u00FCger, and P.A.; writing \u2013 review & editing, L.S. M. Kr\u00FCger, A.M. P.A. J.-W.L. B.B. and M. Koch; visualization, L.S. and C.H.; supervision and project administration, M. Kr\u00FCger; funding acquisition, M. Kr\u00FCger, B.B. and M. Koch. The authors declare no competing interests.

Publisher Copyright:
© 2024 The Author(s)

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