Skeletal muscle regeneration is delayed by reduction in Xin expression: consequence of impaired satellite cell activation?

2012 ◽  
Vol 302 (1) ◽  
pp. C220-C227 ◽  
Author(s):  
Aliyah A. Nissar ◽  
Bart Zemanek ◽  
Rita Labatia ◽  
Daniel J. Atkinson ◽  
Peter F. M. van der Ven ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Tibialis Anterior ◽  
Cell Activation ◽  
Striated Muscle ◽  
Critical Role ◽  
Skeletal Muscle Regeneration ◽  
Actin Binding ◽  
Cell Cycle Reentry ◽  
Satellite Cell Activation

Xin is a striated muscle-specific actin-binding protein whose mRNA expression has been observed in damaged skeletal muscle. Here we demonstrate increased Xin protein expression early postinjury (≤12 h) and localization primarily to the periphery of damaged myofibers. At 1 day postinjury, Xin is colocalized with MyoD, confirming expression in activated satellite cells (SCs). By 5 days postinjury, Xin is evident in newly regenerated myofibers, with a return to preinjury levels by 14 days of regeneration. To determine whether the increased Xin expression is functionally relevant, tibialis anterior muscles of wild-type mice were infected with Xin-short hairpin RNA (shRNA) adenovirus, whereas the contralateral tibialis anterior received control adenovirus (Control). Four days postinfection, muscles were harvested or injured with cardiotoxin and collected at 3, 5, or 14 days thereafter. When compared with Control, Xin-shRNA infection attenuated muscle regeneration as demonstrated by Myh3 expression and fiber areas. Given the colocalization of Xin and MyoD, we isolated single myofibers from infected muscles to investigate the effect of silencing Xin on SC function. Relative to Control, SC activation, but not proliferation, was significantly impaired in Xin-shRNA-infected muscles. To determine whether Xin affects the G0-G1 transition, cell cycle reentry was assessed on infected C2C12 myoblasts using a methylcellulose assay. No difference in reentry was noted between groups, suggesting that Xin contributes to SC activation by means other than affecting G0-G1 transition. Together these data demonstrate a critical role for Xin in SC activation and reduction in Xin expression results in attenuated skeletal muscle repair.

scholarly journals Stra13 regulates satellite cell activation by antagonizing Notch signaling

2007 ◽  
Vol 177 (4) ◽  
pp. 647-657 ◽  
Author(s):  
Hong Sun ◽  
Li Li ◽  
Cécile Vercherat ◽  
Neriman Tuba Gulbagci ◽  
Sujata Acharjee ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Satellite Cell ◽  
Muscle Regeneration ◽  
Cell Activation ◽  
Cellular Proliferation ◽  
Myogenic Differentiation ◽  
Critical Role ◽  
Skeletal Muscle Regeneration ◽  
Notch Activity ◽  
Satellite Cell Activation

Satellite cells play a critical role in skeletal muscle regeneration in response to injury. Notch signaling is vital for satellite cell activation and myogenic precursor cell expansion but inhibits myogenic differentiation. Thus, precise spatial and temporal regulation of Notch activity is necessary for efficient muscle regeneration. We report that the basic helix-loop-helix transcription factor Stra13 modulates Notch signaling in regenerating muscle. Upon injury, Stra13−/− mice exhibit increased cellular proliferation, elevated Notch signaling, a striking regeneration defect characterized by degenerated myotubes, increased mononuclear cells, and fibrosis. Stra13−/− primary myoblasts also exhibit enhanced Notch activity, increased proliferation, and defective differentiation. Inhibition of Notch signaling ex vivo and in vivo ameliorates the phenotype of Stra13−/− mutants. We demonstrate in vitro that Stra13 antagonizes Notch activity and reverses the Notch-imposed inhibition of myogenesis. Thus, Stra13 plays an important role in postnatal myogenesis by attenuating Notch signaling to reduce myoblast proliferation and promote myogenic differentiation.

scholarly journals Septin-7 is indispensable in skeletal muscle regeneration

2021 ◽  
Vol 154 (9) ◽  
Author(s):  
Andrea Telek ◽  
Janos Fodor ◽  
Nora Dobrosi ◽  
Laszlo Szabo ◽  
Monika Gönczi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Division ◽  
Mrna Expression ◽  
Muscle Regeneration ◽  
Tibialis Anterior ◽  
Tibialis Anterior Muscle ◽  
Critical Role ◽  
Skeletal Muscle Regeneration ◽  
The Right

Septins are considered as the fourth component of the cytoskeleton, with septin-7 isoform playing a critical role in myogenic cell division and fusion. Skeletal muscle regeneration is a highly orchestrated process that requires many steps, including proper cell division to achieve functional recovery. Here, the role of septin-7 was investigated in this complex process. To this end, muscle injury was induced in wild type BL6/C57 and septin-7–conditional (mer-Cre-mer) knock-down mice by in vivo BaCl2 injection to the left m. tibialis anterior muscle (TA) of the mice (the right m. tibialis anterior muscle was nontreated control). Mice were sacrificed 4 and 14 d later to reflect the early (monitored by PAX7 level) and late (monitored by myogenin level) phases of muscle regeneration. Western blotting was used to follow the changes of septin-7, PAX7, and myogenin expression at the protein level, while changes of mRNA were detected by qPCR. Morphological differences were visualized by HE staining. Levels of septin-7 protein increased 4 and 14 d after injury in BL6/C57 mice and mRNA expression of SEPT7 showed significant elevation both 4 and 14 d after injection in Cre+ mice only, considered to be a compensatory increase of mRNA expression of SEPT7 in order to ensure the appropriate regeneration process. Furthermore, up-regulation of septin-7 protein was more pronounced on day 14 in both Cre− and Cre+ mice, which may indicate its importance in the later phase of regeneration. Level of PAX7 and myogenin were also increased 4 and 14 d after injury in BL6/C57, Cre−, and Cre+ mice, respectively. Taken together, our data suggest the importance of septin-7 in skeletal muscle regeneration.

scholarly journals Role of proinflammatory cytokines and growth factors in skeletal muscle regeneration

2016 ◽  
Vol 72 (8) ◽  
pp. 472-478
Author(s):  
Marta Milewska ◽  
Katarzyna Grzelkowska-Kowalczyk
Keyword(s):  
Skeletal Muscle ◽  
Growth Factors ◽  
Proinflammatory Cytokines ◽  
Muscle Regeneration ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Muscle Fibers ◽  
Skeletal Muscle Regeneration ◽  
Functional Efficiency

Skeletal muscle healing after injury can be divided into three distinct but overlapping phases. The destruction phase is characterized by rupture followed by necrosis of muscle fibers, formation of hematoma and inflammatory reaction. During the repair phase a necrotic tissue is phagocyted by macrophages, muscle fibers are regenerating and connective tissue scars are formed. The remodeling phase concerns the period when regenerating muscle fibers mature, scar contraction and reorganization occurs and the muscle recovers its functional efficiency. Proinflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and growth factors (FGF, IGF, TGF-β, HGF) play a critical role in all phases of muscle repair. Moreover, chemokines expressed at early stages of myogenesis can regulate the survival and proliferation of myoblasts. Chemokines expressed in vivo in muscle cells can directly influence myogenesis, but can also act in a paracrine manner by recruiting the immune cells (macrophages) to injured skeletal muscles, which is crucial for the regeneration process. Identification of molecules regulating myogenesis, like cytokines, chemokines and growth factors, contributes to the exploration of molecular mechanisms that can improve muscle regeneration after injury, diseases, surgery and increase the effectiveness of cell transplantation.

scholarly journals Krüppel like factor 2 - deficient myeloid cells promote skeletal muscle regeneration after injury

2018 ◽  
Author(s):  
Palanikumar Manoharan ◽  
Taejeong Song ◽  
Tatiana L Radzyukevich ◽  
Sakthivel Sadayappan ◽  
Jerry B Lingrel ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Cell Activation ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Innate Immune ◽  
Skeletal Muscle Regeneration ◽  
Adult Skeletal Muscle ◽  
Complex Interactions ◽  
Elevated Expression

Regeneration of adult skeletal muscle after injury is coordinated by complex interactions between the injured muscle and the innate immune system. Myeloid lineage cells predominate in this process. This study examined the role of Krüppel like factor 2 (KLF2), a zinc-finger transcription factor that regulates myeloid cell activation state, in muscle regeneration. Gastrocnemius muscles of wild-type and myeKlf2-/- mice, which lack KLF2 in all myeloid cells, were subjected to cardiotoxin injury and followed for 21 days. Injured muscles of myeKlf2-/- contained more infiltrating, inflammatory Ly6C+ monocytes, with elevated expression of inflammatory mediators. Infiltrating monocytes matured earlier into pro-inflammatory macrophages with phenotype Ly6C+, CD11b+, F4/80+. Inflammation resolved earlier and progressed to myogenesis, marked by an earlier decline of Ly6C+ macrophages and their replacement with anti-inflammatory Ly6C- populations, in association with elevated expression of factors that resolve inflammation and promote myogenesis. Overall, regeneration was completed earlier. These findings identify myeloid KLF2 as a central regulator of the innate immune response to acute skeletal muscle injury. Manipulating myeloid KLF2 levels may be a useful strategy for accelerating regeneration.

scholarly journals Current Strategies for the Regeneration of Skeletal Muscle Tissue

2021 ◽  
Vol 22 (11) ◽  
pp. 5929
Author(s):  
Emine Alarcin ◽  
Ayca Bal-Öztürk ◽  
Hüseyin Avci ◽  
Hamed Ghorbanpoor ◽  
Fatma Dogan Guzel ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Tissue ◽  
Muscle Regeneration ◽  
Striated Muscle ◽  
Cell Types ◽  
Skeletal Muscle Tissue ◽  
Skeletal Muscle Regeneration ◽  
Muscle Repair ◽  
Clinical Implementation ◽  
Different Cell Types

Traumatic injuries, tumor resections, and degenerative diseases can damage skeletal muscle and lead to functional impairment and severe disability. Skeletal muscle regeneration is a complex process that depends on various cell types, signaling molecules, architectural cues, and physicochemical properties to be successful. To promote muscle repair and regeneration, various strategies for skeletal muscle tissue engineering have been developed in the last decades. However, there is still a high demand for the development of new methods and materials that promote skeletal muscle repair and functional regeneration to bring approaches closer to therapies in the clinic that structurally and functionally repair muscle. The combination of stem cells, biomaterials, and biomolecules is used to induce skeletal muscle regeneration. In this review, we provide an overview of different cell types used to treat skeletal muscle injury, highlight current strategies in biomaterial-based approaches, the importance of topography for the successful creation of functional striated muscle fibers, and discuss novel methods for muscle regeneration and challenges for their future clinical implementation.

scholarly journals FOS licenses early events in stem cell activation driving skeletal muscle regeneration

Cell Reports ◽  
2021 ◽  
Vol 34 (4) ◽  
pp. 108656
Author(s):  
Albert E. Almada ◽  
Naftali Horwitz ◽  
Feodor D. Price ◽  
Alfredo E. Gonzalez ◽  
Michelle Ko ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Muscle Regeneration ◽  
Cell Activation ◽  
Skeletal Muscle Regeneration
Sign in / Sign up

Export Citation Format

Share Document