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Efferocytosis during Skeletal Muscle Regeneration
 
 
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Volume 11
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10.3390/cells11081333
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Article

Regenerating Skeletal Muscle Compensates for the Impaired Macrophage Functions Leading to Normal Muscle Repair in Retinol Saturase Null Mice

by
Nastaran Tarban
1,
Hajnalka Halász
1,
Péter Gogolák
2,
Éva Garabuczi
3,
Alexander R. Moise
4,
Krzysztof Palczewski
5,
Zsolt Sarang
3,† and
Zsuzsa Szondy
3,6,*,†
1
Doctoral School of Molecular Cell and Immune Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
2
Department of Immunology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
3
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
4
Medical Sciences Division, Northern Ontario School of Medicine, Sudbury, ON P3E 2C6, Canada
5
Department of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA 92697, USA
6
Department of Basic Medical Sciences, Faculty of Dentistry, University of Debrecen, 4032 Debrecen, Hungary
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cells 2022, 11(8), 1333; https://doi.org/10.3390/cells11081333
Submission received: 31 January 2022 / Revised: 5 April 2022 / Accepted: 12 April 2022 / Published: 13 April 2022
(This article belongs to the Special Issue Phagocytosis of Apoptotic Cells as Central Driver of the Resolution of Inflammation and the Restoration of Tissue Integrity)
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Abstract

Skeletal muscle repair is initiated by local inflammation and involves the engulfment of dead cells (efferocytosis) by infiltrating macrophages at the injury site. Macrophages orchestrate the whole repair program, and efferocytosis is a key event not only for cell clearance but also for triggering the timed polarization of the inflammatory phenotype of macrophages into the healing one. While pro-inflammatory cytokines produced by the inflammatory macrophages induce satellite cell proliferation and differentiation into myoblasts, healing macrophages initiate the resolution of inflammation, angiogenesis, and extracellular matrix formation and drive myoblast fusion and myotube growth. Therefore, improper efferocytosis results in impaired muscle repair. Retinol saturase (RetSat) initiates the formation of various dihydroretinoids, a group of vitamin A derivatives that regulate transcription by activating retinoid receptors. Previous studies from our laboratory have shown that RetSat-null macrophages produce less milk fat globule-epidermal growth factor-factor-8 (MFG-E8), lack neuropeptide Y expression, and are characterized by impaired efferocytosis. Here, we investigated skeletal muscle repair in the tibialis anterior muscle of RetSat-null mice following cardiotoxin injury. Our data presented here demonstrate that, unexpectedly, several cell types participating in skeletal muscle regeneration compensate for the impaired macrophage functions, resulting in normal muscle repair in the RetSat-null mice.
Keywords: cardiotoxin injury; retinol saturase; neuropeptide Y; MFG-E8; efferocytosis; skeletal muscle repair cardiotoxin injury; retinol saturase; neuropeptide Y; MFG-E8; efferocytosis; skeletal muscle repair

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MDPI and ACS Style

Tarban, N.; Halász, H.; Gogolák, P.; Garabuczi, É.; Moise, A.R.; Palczewski, K.; Sarang, Z.; Szondy, Z. Regenerating Skeletal Muscle Compensates for the Impaired Macrophage Functions Leading to Normal Muscle Repair in Retinol Saturase Null Mice. Cells 2022, 11, 1333. https://doi.org/10.3390/cells11081333

AMA Style

Tarban N, Halász H, Gogolák P, Garabuczi É, Moise AR, Palczewski K, Sarang Z, Szondy Z. Regenerating Skeletal Muscle Compensates for the Impaired Macrophage Functions Leading to Normal Muscle Repair in Retinol Saturase Null Mice. Cells. 2022; 11(8):1333. https://doi.org/10.3390/cells11081333

Chicago/Turabian Style

Tarban, Nastaran, Hajnalka Halász, Péter Gogolák, Éva Garabuczi, Alexander R. Moise, Krzysztof Palczewski, Zsolt Sarang, and Zsuzsa Szondy. 2022. "Regenerating Skeletal Muscle Compensates for the Impaired Macrophage Functions Leading to Normal Muscle Repair in Retinol Saturase Null Mice" Cells 11, no. 8: 1333. https://doi.org/10.3390/cells11081333

APA Style

Tarban, N., Halász, H., Gogolák, P., Garabuczi, É., Moise, A. R., Palczewski, K., Sarang, Z., & Szondy, Z. (2022). Regenerating Skeletal Muscle Compensates for the Impaired Macrophage Functions Leading to Normal Muscle Repair in Retinol Saturase Null Mice. Cells, 11(8), 1333. https://doi.org/10.3390/cells11081333

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