Skip to main content
. 2023 Feb 17;12(4):644. doi: 10.3390/cells12040644

Figure 2.

Figure 2

Influence of cachexia on muscle regeneration and myogenesis. Pax7 maintains self-renewal ability of satellite cells, while TRIM32 and SUMOylation of Pax7 regulate the activation of satellite cells to form progenitor myoblast cells during muscle regeneration. Chemotherapeutics like Dox inhibit satellite cell proliferation via the mTOR pathway, thereby reducing the stem cell pool for muscle regeneration. Upon stimulation by serotonin, the JAK2-STAT3 network is activated, leading to expression of myogenin, a key determinant of myogenesis. On the other hand, IL6-led JAK1-STAT3-STAT1 activation allows downregulation of MyoD1, MEF2 and MHC, which inhibits premature myogenic differentiation and maintains sufficient number of myoblasts. The myogenic progenitor pool is additionally maintained by the expression of S-phase proteins that are regulated by SUMO-modified-G9a and PCAF complex. The surge of pro-inflammatory cytokines in cancer-induced cachexia activates NF-κB and STAT1 signaling that deregulates muscle differentiation through MyoD suppression. Additionally, CIC upregulates ZIP14 thereby leading to accumulation of zinc ion and reduced expression of key myogenic factors. Global SUMOylation is reduced during myogenesis, suggesting a strict regulation and interconnection of the various signaling networks in the process of myogenic differentiation and muscle regeneration. Pointed arrows indicate positive regulation; T shaped arrows indicate negative regulation. CIC: Cancer-induced cachexia; Dox: Doxorubicin; Erk1/2: Extracellular signal-regulated kinase 1/2; G9a: Histone-lysine N-methyltransferase EHMT2; IL-6: Interleukin 6; JAK1: Janus kinase 1; JAK2: Janus kinase 2; MHC: Myosin heavy chain; MEF2: Myocyte-specific enhancer factor 2; mTOR: Mammalian target of rapamycin; MYOD1: Myoblast determination protein 1; MYOG: Myogenin; MYF5: Myogenic factor 5; NFκB: Nuclear factor of kappa light polypeptide gene enhancer in B-cells; Pax7: Paired box protein Pax-7; PCAF: Histone acetyltransferase PCAF; STAT1: Signal transducer and activator of transcription 1; STAT3: Signal transducer and activator of transcription 3; SUMO: Small ubiquitin-related modifier; TRIM32: E3 ubiquitin-protein ligase TRIM32; ZIP14: zinc ion transporter ZRT- and IRT-like protein 14; Zn: Zinc.