PhD Scientific Days 2020

Molecular Sciences I. Posters

Impaired Skeletal Muscle Regeneration and Altered Inflammatory Cytokine and Gdf3 Production in Transglutaminase 2 Knock Out Mouse

Előadó neve

Budai, Zsófia

Előadó munkahelye

Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen

Előadó telefonszáma

+36309049999

Előadó e-mail címe

budai.zsofia@med.unideb.hu

Az előadás címe

Impaired Skeletal Muscle Regeneration and Altered Inflammatory Cytokine and Gdf3 Production in Transglutaminase 2 Knock Out Mouse

Szerző(k) neve és munkahelye

Zsófia Budai1, Nour Al-Zaeed1, Zsuzsa Szondy1,2, Zsolt Sarang1
1Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
2Department of Basic Medical Sciences, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary

Szekció

Molecular Sciences I. Posters

Language of the presentation

English

Section, first choice

Molecular Sciences

Section, second choice

Health Sciences

Összefoglaló szövege

Introduction: Skeletal muscle regeneration is initiated by local inflammation and is accompanied by the removal of dead cells from the injured area. Apoptotic cell phagocytosis regulates the inflammatory program in macrophages by converting the inflammatory phenotype into a healing one. Therefore, abnormal phagocytosis or deregulated inflammation can lead to impaired muscle regeneration.
Aims: Tissue transglutaminase (TG2) is a versatile enzyme playing a role in both the phagocytosis and regulation of inflammation in macrophages; therefore, we aimed to characterize skeletal muscle regeneration in mice in the absence of TG2.
Method: Muscle injury was induced by cardiotoxin injection into the tibialis anterior of TG2+/+ and -/- mice. Laminin immunohistochemistry and DAPI staining were performed on frozen histological sections of isolated muscles to determine the cross-sectional area of myofibers and the number of multinucleated myofibers. We examined the proportion of immune cells invading the regenerating muscle by flow cytometry. Leukocytes (CD45+ cells) were isolated from injured muscles to examine the expression of inflammatory cytokines and growth factors they produce.
Results: We found smaller average myofiber cross-sectional area and higher frequency of smaller fibers in control and regenerating TG2-/- muscles than in the wild type ones. We also observed a lower number of multinucleated myofibers in TG2 KO muscles that may refer to the impaired fusion of myogenic cells. Although the number of infiltrating neutrophils and macrophages is similar during regeneration in wild type and TG2 deficient muscles, the gene expression of TNFα, IL1β, and IL6 pro-inflammatory cytokines at day 2, and the expression of TGFβ1 anti-inflammatory cytokine at day 4 were lower in leukocytes isolated from TG2-/- muscles. Compared to wild type leukocytes the Gdf3 expression was also lower in the absence of TG2.
Conclusion: These results indicate that TG2 affects cytokine and growth factor expression in regenerating skeletal muscle which results in disturbed skeletal muscle development and regeneration.
Funding: OTKA 124244, EFOP-3.6.1-16-2016-00022, EFOP‐3.6.3‐VEKOP‐16‐2017‐00009, GINOP-2.3.2-15- 2016-00006 project

Additional Information

Supervisor: Zsolt Sarang
E-mail address: sarang@med.unideb.hu
EFOP-3.6.3-VEKOP-16-2017-00009 „Az orvos-, egészségtudományi- és gyógyszerészképzés tudományos műhelyeinek fejlesztése

Bemutatás módja

Poszter

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4760

Start

11:26

End

11:29

Authors (legacy)

Zsófia Budai1, Nour Al-Zaeed1, Zsuzsa Szondy1,2, Zsolt Sarang1
1Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
2Department of Basic Medical Sciences, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary