Impaired Skeletal Muscle Development and Regeneration in Transglutaminase 2 Knockout Mice

Skeletal muscle regeneration is triggered by local inflammation and is accompanied by phagocytosis of dead cells at the injury site. Efferocytosis regulates the inflammatory program in macrophages by initiating the conversion of their inflammatory phenotype into the healing one. While pro-inflammato...

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Autores principales:	Zsófia Budai, Nour Al-Zaeed, Péter Szentesi, Hajnalka Halász, László Csernoch, Zsuzsa Szondy, Zsolt Sarang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	transglutaminase 2 muscle repair macrophage myoblast fusion muscle development Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e23d8567257e43fb90004906e1d5d1ab
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spelling	oai:doaj.org-article:e23d8567257e43fb90004906e1d5d1ab2021-11-25T17:11:23ZImpaired Skeletal Muscle Development and Regeneration in Transglutaminase 2 Knockout Mice10.3390/cells101130892073-4409https://doaj.org/article/e23d8567257e43fb90004906e1d5d1ab2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3089https://doaj.org/toc/2073-4409Skeletal muscle regeneration is triggered by local inflammation and is accompanied by phagocytosis of dead cells at the injury site. Efferocytosis regulates the inflammatory program in macrophages by initiating the conversion of their inflammatory phenotype into the healing one. While pro-inflammatory cytokines induce satellite cell proliferation and differentiation into myoblasts, growth factors, such as GDF3, released by healing macrophages drive myoblast fusion and myotube growth. Therefore, improper efferocytosis may lead to impaired muscle regeneration. Transglutaminase 2 (TG2) is a versatile enzyme participating in efferocytosis. Here, we show that TG2 ablation did not alter the skeletal muscle weights or sizes but led to the generation of small size myofibers and to decreased grip force in TG2 null mice. Following cardiotoxin-induced injury, the size of regenerating fibers was smaller, and the myoblast fusion was delayed in the tibialis anterior muscle of TG2 null mice. Loss of TG2 did not affect the efferocytic capacity of muscle macrophages but delayed their conversion to Ly6C<sup>−</sup>CD206<sup>+</sup>, GDF3 expressing cells. Finally, TG2 promoted myoblast fusion in differentiating C2C12 myoblasts. These results indicate that TG2 expressed by both macrophages and myoblasts contributes to proper myoblast fusion, and its ablation leads to impaired muscle development and regeneration in mice.Zsófia BudaiNour Al-ZaeedPéter SzentesiHajnalka HalászLászló CsernochZsuzsa SzondyZsolt SarangMDPI AGarticletransglutaminase 2muscle repairmacrophagemyoblast fusionmuscle developmentBiology (General)QH301-705.5ENCells, Vol 10, Iss 3089, p 3089 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	transglutaminase 2 muscle repair macrophage myoblast fusion muscle development Biology (General) QH301-705.5
spellingShingle	transglutaminase 2 muscle repair macrophage myoblast fusion muscle development Biology (General) QH301-705.5 Zsófia Budai Nour Al-Zaeed Péter Szentesi Hajnalka Halász László Csernoch Zsuzsa Szondy Zsolt Sarang Impaired Skeletal Muscle Development and Regeneration in Transglutaminase 2 Knockout Mice
description	Skeletal muscle regeneration is triggered by local inflammation and is accompanied by phagocytosis of dead cells at the injury site. Efferocytosis regulates the inflammatory program in macrophages by initiating the conversion of their inflammatory phenotype into the healing one. While pro-inflammatory cytokines induce satellite cell proliferation and differentiation into myoblasts, growth factors, such as GDF3, released by healing macrophages drive myoblast fusion and myotube growth. Therefore, improper efferocytosis may lead to impaired muscle regeneration. Transglutaminase 2 (TG2) is a versatile enzyme participating in efferocytosis. Here, we show that TG2 ablation did not alter the skeletal muscle weights or sizes but led to the generation of small size myofibers and to decreased grip force in TG2 null mice. Following cardiotoxin-induced injury, the size of regenerating fibers was smaller, and the myoblast fusion was delayed in the tibialis anterior muscle of TG2 null mice. Loss of TG2 did not affect the efferocytic capacity of muscle macrophages but delayed their conversion to Ly6C<sup>−</sup>CD206<sup>+</sup>, GDF3 expressing cells. Finally, TG2 promoted myoblast fusion in differentiating C2C12 myoblasts. These results indicate that TG2 expressed by both macrophages and myoblasts contributes to proper myoblast fusion, and its ablation leads to impaired muscle development and regeneration in mice.
format	article
author	Zsófia Budai Nour Al-Zaeed Péter Szentesi Hajnalka Halász László Csernoch Zsuzsa Szondy Zsolt Sarang
author_facet	Zsófia Budai Nour Al-Zaeed Péter Szentesi Hajnalka Halász László Csernoch Zsuzsa Szondy Zsolt Sarang
author_sort	Zsófia Budai
title	Impaired Skeletal Muscle Development and Regeneration in Transglutaminase 2 Knockout Mice
title_short	Impaired Skeletal Muscle Development and Regeneration in Transglutaminase 2 Knockout Mice
title_full	Impaired Skeletal Muscle Development and Regeneration in Transglutaminase 2 Knockout Mice
title_fullStr	Impaired Skeletal Muscle Development and Regeneration in Transglutaminase 2 Knockout Mice
title_full_unstemmed	Impaired Skeletal Muscle Development and Regeneration in Transglutaminase 2 Knockout Mice
title_sort	impaired skeletal muscle development and regeneration in transglutaminase 2 knockout mice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e23d8567257e43fb90004906e1d5d1ab
work_keys_str_mv	AT zsofiabudai impairedskeletalmuscledevelopmentandregenerationintransglutaminase2knockoutmice AT nouralzaeed impairedskeletalmuscledevelopmentandregenerationintransglutaminase2knockoutmice AT peterszentesi impairedskeletalmuscledevelopmentandregenerationintransglutaminase2knockoutmice AT hajnalkahalasz impairedskeletalmuscledevelopmentandregenerationintransglutaminase2knockoutmice AT laszlocsernoch impairedskeletalmuscledevelopmentandregenerationintransglutaminase2knockoutmice AT zsuzsaszondy impairedskeletalmuscledevelopmentandregenerationintransglutaminase2knockoutmice AT zsoltsarang impairedskeletalmuscledevelopmentandregenerationintransglutaminase2knockoutmice
_version_	1718412685163364352

Impaired Skeletal Muscle Development and Regeneration in Transglutaminase 2 Knockout Mice

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