Angiotensin Type 2 Receptor Signaling in Satellite Cells Potentiates Skeletal Muscle Regeneration

Yoshida, Tadashi; Huq, Tashfin S.; Delafontaine, Patrick

doi:10.1074/jbc.m114.585521

Cited by 31 publications

(35 citation statements)

References 50 publications

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“…AT 2 R mediates programmed cell death as inhibition of AT 2 R-dependent MKP-1 prevents cell death in PC12W and R3T3 cells (462), which supports a potential involvement of AT 2 R in cancer protection (469). In addition, inhibition of ERK MAPK by AT 2 R appears to induce myoblast differentiation and potentiate skeletal muscle regeneration providing a new therapeutic target in muscle wasting disorders (1211). Within the cardiovascular system, AT 2 R promotes vasorelaxation through PKA-dependent eNOS activation and paracrine signaling through bradykinin/cGMP/NO production (790).…”

Section: B Angiotensin Type 2 Receptormentioning

confidence: 73%

“…In skeletal muscle satellite cells, proliferation is also inhibited by ANG II through AT 1 R-dependent Notch and MyoD suppression (1210). In contrast, AT 2 R stimulation leads to myoblast differentiation and skeletal muscle regeneration (1211). The AT 2 R-mediated muscle regeneration capacity seems blocked in congestive heart failure via suppression of AT 2 R gene transcription (1209).…”

Section: Ang II Signaling In Promoting Skeletal Muscle Atrophymentioning

confidence: 99%

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Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

Forrester

Booz

Sigmund

et al. 2018

Physiological Reviews

735

780

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The renin-angiotensin-aldosterone system plays crucial roles in cardiovascular physiology and pathophysiology. However, many of the signaling mechanisms have been unclear. The angiotensin II (ANG II) type 1 receptor (ATR) is believed to mediate most functions of ANG II in the system. ATR utilizes various signal transduction cascades causing hypertension, cardiovascular remodeling, and end organ damage. Moreover, functional cross-talk between ATR signaling pathways and other signaling pathways have been recognized. Accumulating evidence reveals the complexity of ANG II signal transduction in pathophysiology of the vasculature, heart, kidney, and brain, as well as several pathophysiological features, including inflammation, metabolic dysfunction, and aging. In this review, we provide a comprehensive update of the ANG II receptor signaling events and their functional significances for potential translation into therapeutic strategies. ATR remains central to the system in mediating physiological and pathophysiological functions of ANG II, and participation of specific signaling pathways becomes much clearer. There are still certain limitations and many controversies, and several noteworthy new concepts require further support. However, it is expected that rigorous translational research of the ANG II signaling pathways including those in large animals and humans will contribute to establishing effective new therapies against various diseases.

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Section: B Angiotensin Type 2 Receptormentioning

confidence: 73%

Section: Ang II Signaling In Promoting Skeletal Muscle Atrophymentioning

confidence: 99%

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

Forrester

Booz

Sigmund

et al. 2018

Physiological Reviews

735

780

View full text Add to dashboard Cite

show abstract

“…Indeed, the authors recently found that another Ang II receptor AT2R positively regulates satellite cell differentiation and fusion process. 92 Considering the antagonistic action of AT1R and AT2R, 93 these data indicate that AT1R and AT2R counteract each other and regulate different stages of satellite cell differentiation processes. Furthermore, Acuña et al reported that another angiotensin ligand Ang (1–7) restored muscle strength through inhibition of TGF-β.…”

Section: Ras and Muscle Regenerationmentioning

confidence: 98%

Mechanisms of Cachexia in Chronic Disease States

Yoshida

Delafontaine

2015

The American Journal of the Medical Sciences

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Sarcopenia and cachexia are muscle wasting syndromes associated with aging and with many chronic diseases such as congestive heart failure (CHF), diabetes, cancer, chronic obstructive pulmonary disease and chronic kidney disease (CKD). While mechanisms are complex these conditions are often accompanied by elevated angiotensin II (Ang II). Patients with advanced CHF or CKD often have increased Ang II levels and cachexia, and angiotensin-converting enzyme (ACE) inhibitor treatment improves weight loss. We found that Ang II infusion in rodents leads to skeletal muscle wasting. Ang II increases cytokines and circulating hormones such as tumor necrosis factor-α, interleukin-6, serum amyloid-A and glucocorticoids, which regulate muscle protein synthesis and degradation. Ang II-induced muscle wasting is caused by alterations in insulin-like growth factor-1 signaling, enhanced muscle protein breakdown via the ubiquitin-proteasome system, and decreased appetite resulting from downregulation of hypothalamic orexigenic neuropeptides such as Npy and orexin. Ang II also inhibits 5′ AMP-activated protein kinase (AMPK) activity and disrupts normal energy balance via activation of AMPK phosphatase PP2Cα. Furthermore, Ang II inhibits skeletal muscle stem (satellite) cell proliferation, leading to lowered muscle regenerative capacity. Distinct satellite cell angiotensin receptor subtypes have different effects on different stages of differentiation and are critical for regulation of muscle regeneration. These data suggest that the renin-angiotensin system (RAS) plays a critical role in mechanisms underlying cachexia in chronic disease states, and is a promising target for the treatment of muscle atrophy in patients with diseases such as CHF and CKD.

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“…In contrast, AT2R expression is robustly increased during SC differentiation both in vitro and in vivo. AT2R positively regulates SC differentiation; thus knockdown of AT2R significantly suppressed SC differentiation in vitro and muscle regeneration in vivo (38). These data strongly suggest that Ang II regulates different stages of the SC differentiation process via AT1R and AT2R and that balancing AT1R and AT2R signaling is critical to maintain muscle regenerative capacity mediated by SC function.…”

mentioning

confidence: 71%

An Intronic Enhancer Element Regulates Angiotensin II Type 2 Receptor Expression during Satellite Cell Differentiation, and Its Activity Is Suppressed in Congestive Heart Failure

Yoshida

Delafontaine

2016

Journal of Biological Chemistry

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Patients with advanced congestive heart failure (CHF) or chronic kidney disease often have increased angiotensin II (Ang II) levels and cachexia. We previously demonstrated that Ang II, via its type 1 receptor, causes muscle protein breakdown and apoptosis and inhibits satellite cell (SC) proliferation and muscle regeneration, likely contributing to cachexia in CHF and chronic kidney disease. In contrast, Ang II, via its type 2 receptor (AT2R) expression, is robustly induced during SC differentiation, and it potentiates muscle regeneration. To understand the mechanisms regulating AT2R expression and its potential role in muscle regeneration in chronic diseases, we used a mouse model of CHF and found that muscle regeneration was markedly reduced and that this was accompanied by blunted increase of AT2R expression. We performed AT2R promoter reporter analysis during satellite cell differentiation and found that the 70 bp upstream of the AT2R transcription start site contain a core promoter region, and regions upstream of 70 bp to 3 kbp are dispensable for AT2R induction. Instead, AT2R intron 2 acts as a transcriptional enhancer during SC differentiation. Further deletion/mutation analysis revealed that multiple transcription factor binding sites in the +286/+690 region within intron 2 coordinately regulate AT2R transcription. Importantly, +286/+690 enhancer activity was suppressed in CHF mouse skeletal muscle, suggesting that AT2R expression is suppressed in CHF via inhibition of AT2R intronic enhancer activity, leading to lowered muscle regeneration. Thus targeting intron 2 enhancer element could lead to the development of a novel intervention to increase AT2R expression in SCs and potentiate skeletal muscle regenerative capacity in chronic diseases.

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Angiotensin Type 2 Receptor Signaling in Satellite Cells Potentiates Skeletal Muscle Regeneration

Cited by 31 publications

References 50 publications

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

Mechanisms of Cachexia in Chronic Disease States

An Intronic Enhancer Element Regulates Angiotensin II Type 2 Receptor Expression during Satellite Cell Differentiation, and Its Activity Is Suppressed in Congestive Heart Failure

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