## 3 Results and Discussion
### The Signaling Pathways Underlying Satellite Cell Regulation
#### 3.3.3 Alternative Signaling Pathways
investigated the role of _TGF-\(\beta\)_ activated kinase 1 (_TAKI_) in dystrophic muscle, which is necessary for myofiber regeneration after injury and is activated in adult satellite stem cells. _TAKI_ was reported to be activated in response to _TRAF6_ polyubiquitination, which then engages the Nuclear Factor kappa-light-chain-enhancer of Activated B cells (NF-\(\kappa\)B) and the MAPK signaling pathways [83; 84]. NF-\(\kappa\)B is one of the important signaling pathways activated through _TAKI_-dependent mechanisms. They revealed that satellite-cell-specific _TAKI_ knock-out mice (TAK1\({}^{\text{scko}}\)) had reduced muscle regeneration, with a decrease in the number and size of centrally nucleated fibers as wellas cell arrest with the reduction in the G2/M phase in the cell cycle. _TAK1_ inactivation inhibited regenerative myogenesis in mice by reducing fiber size and the number of myogenic factors (embryonic-Myosin Heavy Chin (_eMyHC_), _MyF5_, _MyoD_ and _MyoG_ in both injured and uninjured mice models, indicating that myogenesis was reduced during early regeneration. _TAK1_ is necessary for preserving the satellite stem cell pool in the skeletal muscle of adults, and its inactivation compromises muscle regenerative capability, which causes muscle wasting. The Pax7\(-\)/MyoD+ cell population significantly increased in TAK1\({}^{\text{sckO}}\) mice, while the Pax7\(+\)/MyoD+ activated stem cell population decreased, explaining that _TAK1_ is essential for satellite cell generation, proliferation, and self-renewal; however, it does not regulate _MyoD_ expression while inhibiting premature progression in the myogenic cell lineage. Moreover, _TAK1_ is crucial for satellite cell survival, and _TAK1_ disruption can result in necroptosis. The increase in reactive oxygen species (ROS) in TAK1\({}^{\text{sckO}}\) mice was shown by the rescue of the majority of cell deaths, Pax7\(+\) proliferation, and _MyoD_ expression in satellite cells, by the necroptosis inhibitor. Therefore, _TAK1_ inactivation inhibits NF-kB pathways in satellite cells, leading to poor survival and proliferation, and it is essential for satellite cell proliferation and survival, as well as regenerative myogenesis. Additionally, _TAK1_ is the key for cellular homeostasis, and reduced proliferation of satellite cells in TAK1\({}^{\text{sckO}}\) mice may be due to the diminished sustainability and increased mortality of satellite cells. Table 4 compiles the findings of the selected articles discussed above. \begin{table}
\begin{tabular}{c c c c c} \hline \hline
**No. ** **Author(s)** & **Year of Publication** & **Animal Model** & **Signaling Pathways** & & **Key Findings** \\ \hline \multirow{4}{*}{1} & \multirow{4}{*}{2020} & & 1. & The study confirmed that _MyoG_ is a crucial regulator of \\  & & & & adult myofiler growth and muscle stem cell homeostasis. \\  & & & 2. & Loss of _MyoG_ causes mTORC1 signaling activation in \\  & & & myofo\({}^{\text{h,3D}}\) mutant allele, & & & \\  & & Myo\({}^{\text{h,4  
\begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**No. Author(s)** & \ \begin{tabular}{c} **Year of** \\ **Publication** \\ \end{tabular}  & **Animal Model** & \begin{tabular}{c} **Signaling** \\ **Pathways** \\ \end{tabular}  & \multicolumn{2}{c}{**Key Findings**} \\ \hline
3 & \ \begin{tabular}{c} **Hindi \&** \\ **[PERSON]** \\ **[35]** \\ \end{tabular}  & 2016 &
\begin{tabular}{c} _Paz7 CrreR_