Cilia‐Mediated Insulin/Akt and ST2/JNK Signaling Pathways Regulate the Recovery of Muscle Injury

Yamakawa, Daishi; Tsuboi, Junya; Kasahara, Kousuke; Matsuda, Chise; Nishimura, Yuhei; Kodama, Tatsuhiko; Katayama, Naoyuki; Watanabe, Masatoshi; Inagaki, Masaki

doi:10.1002/advs.202202632

Cited by 7 publications

(4 citation statements)

References 56 publications

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“…In this study, we found that overexpression of GPX2 increases JNK, ERK, and p-p38 expression in proliferation process of porcine skeletal muscle cells. Several studies have reported that cell proliferation was promoted via activation of JNK [ 48 , 49 ]. Similar to this, it has been shown that ERK activation mediates cell proliferation and cell cycle progression in myoblasts [ 50 ], and early ERK signal was a crucial factor in determining the proliferation of muscle stem cells [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of GPX2 gene regulates the development of porcine preadipocytes and skeletal muscle cells through MAPK signaling pathway

Zhang,

Wang,

Qin

et al. 2024

PLoS ONE

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Glutathione peroxidase 2 (GPX2) is a selenium-dependent enzyme and protects cells against oxidative damage. Recently, GPX2 has been identified as a candidate gene for backfat and feed efficiency in pigs. However, it is unclear whether GPX2 regulates the development of porcine preadipocytes and skeletal muscle cells. In this study, adenoviral gene transfer was used to overexpress GPX2. Our findings suggest that overexpression of GPX2 gene inhibited proliferation of porcine preadipocytes. And the process is accompanied by the reduction of the p-p38. GPX2 inhibited adipogenic differentiation and promoted lipid degradation, while ERK1/2 was reduced and p-p38 was increased. Proliferation of porcine skeletal muscle cells was induced after GPX2 overexpression, was accompanied by activation in JNK, ERK1/2, and p-p38. Overexpression methods confirmed that GPX2 has a promoting function in myoblastic differentiation. ERK1/2 pathway was activated and p38 was suppressed during the process. This study lays a foundation for the functional study of GPX2 and provides theoretical support for promoting subcutaneous fat reduction and muscle growth.

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Section: Discussionmentioning

confidence: 99%

Overexpression of GPX2 gene regulates the development of porcine preadipocytes and skeletal muscle cells through MAPK signaling pathway

Zhang,

Wang,

Qin

et al. 2024

PLoS ONE

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“…Moreover, MAPK signaling pathway were enriched in adipogenic differentiation of FAPs after CLAs treatment. Previous studies have discovered JNK had negative effects on regulating the adipogenic differentiation of human mesenchymal stem cells(Jang et al, 2015) and FAPs could prevent skeletal muscle regeneration after muscle injury by ST2/JNK signaling pathways(Yamakawa et al, 2023). In this study, we found CLAs may promote FAPs directed differentiation into SCD + /DGAT2 + adipocytes via inhibiting JNK signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Single-nucleus transcriptomics reveal the cytological mechanism of conjugated linoleic acids in regulating intramuscular fat deposition

Wang,

Liu,

Zhang

et al. 2024

Preprint

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Conjugated linoleic acids (CLAs) can serve as a nutritional intervention to regulate quality, function and fat infiltration in skeletal muscles but the specific cytological mechanisms are still unknown. Here, we applied single-nucleus RNA-sequencing (snRNA-seq) to characterize the cytological mechanism of CLAs regulates fat infiltration in skeletal muscles based on pig models. We investigated the regulatory effects of CLAs on cell populations and molecular characteristics in pig muscles and found CLAs could promote the transformation of fast glycolytic myofibers into slow oxidative myofibers. We also observed three subpopulations including SCD+/DGAT2+, FABP5+/SIAH1+, and PDE4D+/PDE7B+subclusters in adipocytes and CLAs could increase the percentage of SCD+/DGAT2+adipocytes. RNA velocity analysis showed FABP5+/SIAH1+and PDE4D+/PDE7B+adipocytes could differentiate into SCD+/DGAT2+adipocytes. We further verified the differentiated trajectory of mature adipocytes and identified PDE4D+/PDE7B+adipocytes could differentiate into SCD+/DGAT2+and FABP5+/SIAH1+adipocytes by using high IMF content Laiwu pig models. The cell-cell communication analysis identified the interaction network between adipocytes and other subclusters such as fibro/adipogenic progenitors (FAPs). Pseudotemporal trajectory analysis and RNA velocity analysis also showed FAPs could differentiate into PDE4D+/PDE7B+preadipocytes and we discovered the differentiated trajectory of preadipocytes into mature adipocytes. Besides, we found CLAs could promote FAPs differentiate into SCD+/DGAT2+adipocytes via inhibiting c-Jun N-terminal kinase (JNK) signalling pathwayin vitro. This study provides a foundation for regulating fat infiltration in skeletal muscles by using nutritional strategies and provides potential opportunities to serve pig as an animal model to study human fat infiltrated diseases.

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“…Targeting proteins that can bind and activate AURKA in selective cells may be desirable to maximize therapeutic efficacy and minimize side effects. TCHP may be a candidate for this approach because the knockout mice are viable and show resistance to high-fat diet-induced obesity and increased regeneration following skeletal muscle injuries ( Yamakawa et al, 2021 ; Yamakawa et al, 2022 ). Chemicals can be developed that inhibit the interaction between AURKA and the binding partner or degrade ciliary proteins by proteolysis-targeting chimeras ( Janeček et al, 2016 ; Bagka et al, 2022 ).…”

Section: Ciliogenesis As the Therapeutic Targetmentioning

confidence: 99%

Recent advances in the understanding of cilia mechanisms and their applications as therapeutic targets

Saito,

Otsu,

Miyadera

et al. 2023

Front. Mol. Biosci.

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The primary cilium is a single immotile microtubule-based organelle that protrudes into the extracellular space. Malformations and dysfunctions of the cilia have been associated with various forms of syndromic and non-syndromic diseases, termed ciliopathies. The primary cilium is therefore gaining attention due to its potential as a therapeutic target. In this review, we examine ciliary receptors, ciliogenesis, and ciliary trafficking as possible therapeutic targets. We first discuss the mechanisms of selective distribution, signal transduction, and physiological roles of ciliary receptors. Next, pathways that regulate ciliogenesis, specifically the Aurora A kinase, mammalian target of rapamycin, and ubiquitin-proteasome pathways are examined as therapeutic targets to regulate ciliogenesis. Then, in the photoreceptors, the mechanism of ciliary trafficking which takes place at the transition zone involving the ciliary membrane proteins is reviewed. Finally, some of the current therapeutic advancements highlighting the role of large animal models of photoreceptor ciliopathy are discussed.

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Cilia‐Mediated Insulin/Akt and ST2/JNK Signaling Pathways Regulate the Recovery of Muscle Injury

Cited by 7 publications

References 56 publications

Overexpression of GPX2 gene regulates the development of porcine preadipocytes and skeletal muscle cells through MAPK signaling pathway

Overexpression of GPX2 gene regulates the development of porcine preadipocytes and skeletal muscle cells through MAPK signaling pathway

Single-nucleus transcriptomics reveal the cytological mechanism of conjugated linoleic acids in regulating intramuscular fat deposition

Recent advances in the understanding of cilia mechanisms and their applications as therapeutic targets

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