Follistatin-like 1, a Secreted Muscle Protein, Promotes Endothelial Cell Function and Revascularization in Ischemic Tissue through a Nitric-oxide Synthase-dependent Mechanism

Ouchi, Noriyuki; Oshima, Yoshifumi; Ohashi, Koji; Higuchi, Akiko; Ikegami, Chiaki; Izumiya, Yasuhiro; Walsh, Kenneth

doi:10.1074/jbc.m803440200

Cited by 273 publications

(270 citation statements)

References 37 publications

(44 reference statements)

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“…We previously reported several factors secreted by muscle that are increased by Akt1 overexpression. 18,43 In the UUO model, we found that myogenic activation of Akt upregulated serum levels of stromal cell-derived factor-1, IL-10, and IL-17, which are known to activate eNOS. 44,45 Further studies will be required to determine whether these factors are involved in renal eNOS activation and renoprotective properties of Akt1-mediated skeletal muscle growth.…”

Section: Discussionmentioning

confidence: 96%

Akt1-Mediated Fast/Glycolytic Skeletal Muscle Growth Attenuates Renal Damage in Experimental Kidney Disease

Hanatani

Izumiya

Araki

et al. 2014

Journal of the American Society of Nephrology

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Muscle wasting is frequently observed in patients with kidney disease, and low muscle strength is associated with poor outcomes in these patients. However, little is known about the effects of skeletal muscle growth per se on kidney diseases. In this study, we utilized a skeletal muscle-specific, inducible Akt1 transgenic (Akt1 TG) mouse model that promotes the growth of functional skeletal muscle independent of exercise to investigate the effects of muscle growth on kidney diseases. Seven days after Akt1 activation in skeletal muscle, renal injury was induced by unilateral ureteral obstruction (UUO) in Akt1 TG and wild-type (WT) control mice. The expression of atrogin-1, an atrophy-inducing gene in skeletal muscle, was upregulated 7 days after UUO in WT mice but not in Akt1 TG mice. UUO-induced renal interstitial fibrosis, tubular injury, apoptosis, and increased expression of inflammatory, fibrosis-related, and adhesion molecule genes were significantly diminished in Akt1 TG mice compared with WT mice. An increase in the activating phosphorylation of eNOS in the kidney accompanied the attenuation of renal damage by myogenic Akt1 activation. Treatment with the NOS inhibitor L-NAME abolished the protective effect of skeletal muscle Akt activation on obstructive kidney disease. In conclusion, Akt1-mediated muscle growth reduces renal damage in a model of obstructive kidney disease. This improvement appears to be mediated by an increase in eNOS signaling in the kidney. Our data support the concept that loss of muscle mass during kidney disease can contribute to renal failure, and maintaining muscle mass may improve clinical outcome.

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Section: Discussionmentioning

confidence: 96%

Akt1-Mediated Fast/Glycolytic Skeletal Muscle Growth Attenuates Renal Damage in Experimental Kidney Disease

Hanatani

Izumiya

Araki

et al. 2014

Journal of the American Society of Nephrology

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“…Most interestingly, it is upregulated via Akt signalling. Ouchi et al have proposed that FSTL1 can be designated as a myokine that acts on vascular endothelial cells [130]. In murine skeletal muscle, overexpression of FSTL1 was shown to promote endothelial cell function and revascularisation in ischaemic tissue.…”

Section: Key Facts: Myokines As Therapeutic Targetsmentioning

confidence: 99%

“…However, skeletal muscle is not the only tissue to express and release FSTL1. Proteomic approaches have identified FSTL1 in the supernatant fraction of primary human adipocytes [132], in the supernatant fraction of human endothelial cells [130] and in lysates of murine cardiac myocytes [133].…”

Section: Key Facts: Myokines As Therapeutic Targetsmentioning

confidence: 99%

Myokines in insulin resistance and type 2 diabetes

et al. 2014

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Skeletal muscle represents the largest organ of the body in non-obese individuals and is now considered to be an active endocrine organ releasing a host of so-called myokines. These myokines are part of a complex network that mediates communication between muscle, the liver, adipose tissue, the brain and other organs. Recent data suggest that myokines regulated by muscle contraction may play a key role in mediating the health-promoting effects of regular physical activity. Although hundreds of myokines have recently been described in proteomic studies, we currently have a rather limited knowledge of the specific role these myokines play in the prevention of insulin resistance, inflammation and associated metabolic dysfunction. Several myokines are known to have both local and endocrine functions, but in many cases the contribution of physical activity to the systemic level of these molecules remains as yet unexplored. Very recently, novel myokines such as irisin, which is thought to induce a white to brown shift in adipocytes, have gained considerable interest as potential therapeutic targets. In this review, we summarise the most recent findings on the role of myokines in the regulation of substrate metabolism and insulin sensitivity. We further explore the role of myokines in the regulation of inflammation and provide a critical assessment of irisin and other myokines regarding their potential as therapeutic targets.

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“…Secreted by skeletal muscle fiber in response to exercise, IL-6 has been shown to improve whole-body insulin sensitivity and dampen inflammation, providing a link between exercise and the improvement in systemic metabolic parameters (15,16). In mice, skeletal muscle-derived Fstl-1 promotes endothelial cell function and revascularization in ischemic tissue (10). Elevated serum levels of IL-15 via transgenic expression in mouse skeletal muscle reduce fat mass and decrease adiposity in response to high-fat feeding (13).…”

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confidence: 99%

Myonectin (CTRP15), a Novel Myokine That Links Skeletal Muscle to Systemic Lipid Homeostasis

Seldin

Peterson

Byerly

et al. 2012

Journal of Biological Chemistry

327

406

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Background: Skeletal muscle-derived myokines modulate metabolic, inflammatory, and other processes. Results: Myonectin, a novel myokine whose expression and circulating levels are regulated by diet, metabolic state, and exercise, functions to control lipid metabolism. Conclusion: Myonectin is a potential nutrient-responsive metabolic regulator secreted by muscle. Significance: Myonectin links muscle to systemic lipid metabolism via its action on adipocytes and hepatocytes, providing insight into complex tissue cross-talk.

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Follistatin-like 1, a Secreted Muscle Protein, Promotes Endothelial Cell Function and Revascularization in Ischemic Tissue through a Nitric-oxide Synthase-dependent Mechanism

Cited by 273 publications

References 37 publications

Akt1-Mediated Fast/Glycolytic Skeletal Muscle Growth Attenuates Renal Damage in Experimental Kidney Disease

Akt1-Mediated Fast/Glycolytic Skeletal Muscle Growth Attenuates Renal Damage in Experimental Kidney Disease

Myokines in insulin resistance and type 2 diabetes

Myonectin (CTRP15), a Novel Myokine That Links Skeletal Muscle to Systemic Lipid Homeostasis

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