2. Academic Validation
  3. Myofiber directs macrophages IL-10-Vav1-Rac1 efferocytosis pathway in inflamed muscle following CTX myoinjury by activating the intrinsic TGF-β signaling

Myofiber directs macrophages IL-10-Vav1-Rac1 efferocytosis pathway in inflamed muscle following CTX myoinjury by activating the intrinsic TGF-β signaling

  • Cell Commun Signal. 2023 Jul 4;21(1):168. doi: 10.1186/s12964-023-01163-8.
Zhaohong Liao # 1 2,  Haiqiang Lan # 1,  Xiaoting Jian # 1,  Jingwen Huang 1,  Han Wang 1,  Jijie Hu 3,  Hua Liao 4
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering; Department of Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • 2 Department of Laboratory Medicine, School of Medicine, Foshan University, Foshan, 528000, China.
  • 3 Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. [email protected].
  • 4 Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering; Department of Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China. [email protected].
  • # Contributed equally.
PMID: 37403092 DOI: 10.1186/s12964-023-01163-8
Abstract

Background: To explore the role of skeletal muscle specific TGF-β signaling on macrophages efferocytosis in inflamed muscle caused by Cardiotoxin (CTX) injection.

Methods: CTX myoinjury was manipulated in TGF-βr2flox/flox (control) mice or transgenic mice with TGF-β Receptor 2 (TGF-βr2) being specifically deleted in skeletal muscle (SM TGF-βr2-/-). Gene levels of TGF-β signal molecules, special inflammatory mediators in damaged muscle or in cultured and differentiated myogenic precursor cells (MPC-myotubes) were monitored by transcriptome microarray or qRT-PCR. TGF-β pathway molecules, myokines and embryonic Myosin heavy chain in regenerating myofibers, the phenotype and efferocytosis of macrophages were evaluated by immunofluorescence, immunoblotting, Luminex, or FACS analysis. In vitro apoptotic cells were prepared by UV-irradiation.

Results: In control mice, TGF-β-Smad2/3 signaling were significantly up-regulated in regenerating centronuclear myofibers after CTX-myoinjury. More severe muscle inflammation was caused by the deficiency of muscle TGF-β signaling, with the increased number of M1, but the decreased number of M2 macrophages. Notably, the deficiency of TGF-β signaling in myofibers dramatically affected on the ability of macrophages to conduct efferocytosis, marked by the decreased number of Annexin-V-F4/80+Tunel+ macrophages in inflamed muscle, and the impaired uptake of macrophages to PKH67+ apoptotic cells transferred into damaged muscle. Further, our study suggested that, the intrinsic TGF-β signaling directed IL-10-Vav1-Rac1 efferocytosis signaling in muscle macrophages.

Conclusions: Our data demonstrate that muscle inflammation can be suppressed potentially by activating the intrinsic TGF-β signaling in myofibers to promote IL-10 dependent-macrophages efferocytosis. Video Abstract.

Keywords

IL-10; Macrophages efferocytosis; Myoinjury; TGF-β signaling.

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