Atx regulates skeletal muscle regeneration via LPAR1 and promotes hypertrophy

Ray, Rashmi; Sunita, S.; Aidinis, Vassilis; Rai, Vivek

doi:10.1016/j.celrep.2021.108809

Cited by 15 publications

(28 citation statements)

References 33 publications

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“…In this step, muscle stem or satellite cells are isolated from skeletal muscle tissues of mice, cultured to form myoblasts and differentiated further to generate hypertrophic myotubes. LPA is added to differentiating satellite cells to induce hypertrophy as reported in Ray et al. (2021) .…”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

“…Skeletal muscle regeneration is induced by initiating skeletal muscle injury by the intramuscular injection of cardiotoxin (CTX), a snake venom toxin that induces myofiber damage and a strong regenerative response ( Chargé and Rudnicki, 2004 ; Goddeeris et al, 2013 ; Price et al, 2014 ). Here we describe the steps in induction of muscle injury and initiation of accelerated repair by injecting LPA to regenerating muscles as reported in Ray et al. (2021) .…”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

“…This protocol can be used to study the mechanisms associated with accelerated muscle repair and hypertrophy. For complete details on the use and execution of this protocol, please refer to Ray et al. (2021) .…”

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confidence: 99%

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Protocol for accelerated skeletal muscle regeneration and hypertrophic muscle formation in mice

Ray

Rai

2022

STAR Protocols

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Summary The skeletal muscle system is the major organ associated with movement of the body. Myogenesis and regeneration induced post-injury contribute to muscle formation and maintenance. Here, we provide detailed protocol for the accelerated repair of injured skeletal muscles and generation of hypertrophic muscle fibers. This protocol includes cardiotoxin induced muscle injury and also describes isolation of satellite cells from skeletal muscle tissues of mice. This protocol can be used to study the mechanisms associated with accelerated muscle repair and hypertrophy. For complete details on the use and execution of this protocol, please refer to Ray et al. (2021) .

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Section: Step-by-step Methods Detailsmentioning

confidence: 99%

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

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Protocol for accelerated skeletal muscle regeneration and hypertrophic muscle formation in mice

Ray

Rai

2022

STAR Protocols

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“…The most recent research has revealed that ATX allows fundamental human activity to be conducted and participates in homeostasis and the development of pathological conditions [18,19]. ATX is required during the restoration of muscles by satellite cells, while ATX conditioned ablation or drug inhibition has been shown to impair muscle regeneration [20]. Recent studies have shown that the reconstruction of cartilage in OA temporomandibular joints using extracellular vesicles is mediated via the ATX-YAP signaling pathway [8].…”

Section: Inhibition Of Atx Promoted Lysosomalnumber and Acidity In Oa...mentioning

confidence: 99%

Inhibition of Autotaxin Induces Imbalance of Chondrocyte Metabolism and Suppression of Autophagic Flux in Osteoarthritis

Dai

Wang

Zhang

et al. 2022

Preprint

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Background: Osteoarthritis (OA) is a degenerative joint disease that couldn’t be cured by drugs. Autotaxin (ATX), which is a secretory glycoprotein related to physiological and pathological processes may possibly participate in the appropriate formation of cartilage. However, the role and specific mechanism of ATX in OA remain unclear. The present study aimed to explore the metabolism of chondrocytes and the mechanism of action of ATX in OA.Results: In OA chondrocytes, catabolism increased and anabolism decreased. Inhibition of ATX triggered imbalanced metabolism according to the overexpression of a disintegrin and metalloproteinase with thrombospondin type 1 motif-5 (ADAMTS-5) and matrix metalloproteinase 13 (MMP13) and downregulation of collagen type II alpha 1 (COL2A1). Inhibition of ATX also caused the expression of mechanistic target of rapamycin (mTOR) declined while the expression of P62/ SQSTM1 and the microtubule-associated protein light chain 3- (LC3-) II-to-LC3-I ratio were upregulated which illustrated a blockade autophagic flux. The acidity of the lysosomes was dramatically enhanced according to LysoTracker green staining. Infection with Mcherry-EGFP-LC3 adenovirus and measurement of immunofluorescence were performed to detect the formation of autolysosomes. And it was observed that the fusion of autophagosomes and lysosomes was blocked, resulting in the obstruction of autophagic flux.Conclusions: These data indicate that inhibition of ATX expression in chondrocytes resulted in abnormal metabolism and impaired autophagic flux via blockade of autophagosome and lysosome fusion, revealing a novel mechanism that regulated chondrocytes in OA which may provide a new target for the treatment of OA in the future.

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“…Several studies have examined the effect of the LPA1/3 antagonist, specifically Ki16425, administration on energy homeostasis and glucose metabolism in mice with genetic or diet-induced obesity. Based on mRNA analysis, using murine tissues, LPA1 and LPA3 appear to be expressed to a varying extent in insulin target tissues, including WAT, liver, skeletal muscle, and heart [76,79,80]. It has also been shown that LPA receptor levels in these tissues can markedly change during obesity in mice and humans [76,79].…”

Section: Studies Using Pharmacological Lpa Receptor and Atx Modulators And In Situ Atx Silencingmentioning

confidence: 99%

Autotaxin-LPA-LPP3 Axis in Energy Metabolism and Metabolic Disease

Jose

Kienesberger

2021

IJMS

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Besides serving as a structural membrane component and intermediate of the glycerolipid metabolism, lysophosphatidic acid (LPA) has a prominent role as a signaling molecule through its binding to LPA receptors at the cell surface. Extracellular LPA is primarily produced from lysophosphatidylcholine (LPC) through the activity of secreted lysophospholipase D, autotaxin (ATX). The degradation of extracellular LPA to monoacylglycerol is mediated by lipid phosphate phosphatases (LPPs) at the cell membrane. This review summarizes and interprets current literature on the role of the ATX-LPA-LPP3 axis in the regulation of energy homeostasis, insulin function, and adiposity at baseline and under conditions of obesity. We also discuss how the ATX-LPA-LPP3 axis influences obesity-related metabolic complications, including insulin resistance, fatty liver disease, and cardiomyopathy.

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Atx regulates skeletal muscle regeneration via LPAR1 and promotes hypertrophy

Abstract: Highlights d Autotaxin (Atx) is a key regulator of satellite cell function d Conditional deletion of Atx in satellite cells impairs skeletal muscle regeneration d Atx-LPA induces S6K-mTOR signaling via LPAR1 d Atx-LPA promotes muscle hypertrophy

Cited by 15 publications

References 33 publications

Protocol for accelerated skeletal muscle regeneration and hypertrophic muscle formation in mice

Protocol for accelerated skeletal muscle regeneration and hypertrophic muscle formation in mice

Inhibition of Autotaxin Induces Imbalance of Chondrocyte Metabolism and Suppression of Autophagic Flux in Osteoarthritis

Autotaxin-LPA-LPP3 Axis in Energy Metabolism and Metabolic Disease

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