Endogenous galectin-3 is required for skeletal muscle repair

Abstract

Skeletal muscle has the intrinsic ability to self-repair through a multifactorial process, but many aspects of its cellular and molecular mechanisms are not fully understood. There is increasing evidence that some members of the mammalian β-galactoside-binding protein family (galectins) are involved in the muscular repair process (MRP), including galectin-3 (Gal-3). However, there are many questions about the role of this protein on muscle self-repair. Here, we demonstrate that endogenous Gal-3 is required for: i) muscle repair in vivo using a chloride-barium myolesion mouse model, and ii) mouse primary myoblasts myogenic programming. Injured muscle from Gal-3 knockout mice (GAL3KO) showed persistent inflammation associated with compromised muscle repair and the formation of fibrotic tissue on the lesion site. In GAL3KO mice, osteopontin expression remained high even after 7 and 14 days of the myolesion, while MyoD and myogenin had decreased their expression. In GAL3KO mouse primary myoblast cell culture, Pax7 detection seems to sustain even when cells are stimulated to differentiation and MyoD expression is drastically reduced. The detection and temporal expression levels of these transcriptional factors appear to be altered in Gal-3-deficient myoblast. Gal-3 expression in WT states, both in vivo and in vitro, in sarcoplasm/cytoplasm and myonuclei; as differentiation proceeds, Gal-3 expression is drastically reduced, and its location is confined to the sarcolemma/plasma cell membrane. We also observed a change in the temporal–spatial profile of Gal-3 expression and muscle transcription factors levels during the myolesion. Overall, these results demonstrate that endogenous Gal-3 is required for the skeletal muscle repair process.

Single-cell and spatial transcriptomics identify a macrophage population associated with skeletal muscle fibrosis

“…The emergence of gal-3 + macrophages has also been reported in the brain, lung, heart, aorta and liver when homeostasis is disrupted in these organs (65,(72)(73)(74)(75)(76). Studies of barium chloride-induced muscle injury or autologous muscle grafting in mice showed that galectin-3 and Spp1 promote regeneration in acute settings (77)(78)(79). These findings suggest that muscle regeneration and fibrosis share common pathways of regulation, and a temporal-dependent mechanism partly determines whether Spp1 and galectin-3 promote regeneration or fibrosis.…”

Delivery of a tissue derived extracellular matrix gel modulates early fibro-adipogenic cell behavior and improves recovery following both acute and chronic atrophy muscle injury

“…LGALS3 which aids in the fusion and differentiation of myoblasts during muscle repair and regeneration were increased by 4.6, 4.8, and 3 folds in 7DPI transcripts, 3 DPI and 14DPI proteins abundance respectively 40,41 . Similar increases were observed for RAC2 which is essential in myotube formation and regulation of hypertrophy 42,43 .…”

Controlling differentiation of stem cells via bioactive disordered cues

“…40,92 BMPs induce the differentiation of mesenchymal cells towards chondrogenic and osteogenic lineages. 8,93 The differentiation of hMSCs and progenitors towards the osteoblastic lineage is usually accomplished in response to BMP proteins or their mimetic peptides. BMPs interact with BMPR-I and BMPR-II receptors leading to the phosphorylation of BMPR-I by BMPR-II, which in turn activates Smad 1/5/8 signalling pathways.…”