Interleukin‐15 receptor subunit alpha regulates interleukin‐15 localization and protein expression in skeletal muscle cells

Yoshida, Shigetomo; Fujimoto, Taku; Takahashi, Toshimasa; Sugimoto, Ken; Akasaka, Hiroshi; Tanaka, Minoru; Huang, Yibin; Yasunobe, Yukiko; Xie, Kaizhou; Ohnishi, Yuri; Minami, Tomohiro; Takami, Yoichi; Yamamoto, Kōichi; Rakugi, Hiromi

doi:10.1113/ep090205

Cited by 7 publications

(4 citation statements)

References 44 publications

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“…Both markers have been implicated in kidney disease ( 36 , 37 ). though with different mechanisms being involved for the role of these molecules in renal failure ( 38 – 40 ).…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, we report very different patterns of these two markers in the comparator groups with, for example, IL-15RA being lower in pre-frail elderly individuals than in healthy controls, unlike the situation seen with FGF-23. 1L-15 has been shown to be reduced in ageing animal models and given that IL-1RA regulates the localization in immune cells of IL-15 ( 40 , 61 ). This might explain why IL-15RA is lower in a pre-frail or frail individuals than in healthy controls.…”

Section: Discussionmentioning

confidence: 99%

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Preoperative inflammatory biomarkers reveal renal involvement in postsurgical mortality in hip fracture patients: an exploratory study

Valdes,

Ikram,

Taylor

et al. 2024

Front. Immunol.

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BackgroundHip fractures in frail patients result in excess mortality not accounted for by age or comorbidities. The mechanisms behind the high risk of mortality remain undetermined but are hypothesized to be related to the inflammatory status of frail patients.MethodsIn a prospective observational exploratory cohort study of hospitalized frail hip fracture patients, 92 inflammatory markers were tested in pre-operative serum samples and markers were tested against 6-month survival post-hip fracture surgery and incidence of acute kidney injury (AKI). After correcting for multiple testing, adjustments for comorbidities and demographics were performed on the statistically significant markers.ResultsOf the 92 markers tested, circulating levels of fibroblast growth factor 23 (FGF-23) and interleukin-15 receptor alpha (IL15RA), both involved in renal disease, were significantly correlated with 6-month mortality (27.5% overall) after correcting for multiple testing. The incidence of postoperative AKI (25.4%) was strongly associated with 6-month mortality, odds ratio = 10.57; 95% CI [2.76–40.51], and with both markers plus estimated glomerular filtration rate (eGFR)– cystatin C (CYSC) but not eGFR-CRE. The effect of these markers on mortality was significantly mediated by their effect on postoperative AKI.ConclusionHigh postoperative mortality in frail hip fracture patients is highly correlated with preoperative biomarkers of renal function in this pilot study. The effect of preoperative circulating levels of FGF-23, IL15RA, and eGFR-CYSC on 6-month mortality is in part mediated by their effect on postoperative AKI. Creatinine-derived preoperative renal function measures were very poorly correlated with postoperative outcomes in this group.

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“…Both markers have been implicated in kidney disease ( 36 , 37 ). though with different mechanisms being involved for the role of these molecules in renal failure ( 38 – 40 ).…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Preoperative inflammatory biomarkers reveal renal involvement in postsurgical mortality in hip fracture patients: an exploratory study

Valdes,

Ikram,

Taylor

et al. 2024

Front. Immunol.

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“…IL-15RA is an important component of the IL-15 proinflammatory signalling that occurs in muscles after exercise. 23 , 24 In the skeletal system, IL-15RA plays a cell-autonomous role in osteoblast function and bone mineralization. 25 IL-15RA SNPs are associated with susceptibility to ossification of the posterior longitudinal ligament of the spine.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome-wide association study reveals candidate causal genes for lumbar spinal stenosis

Zeng

et al. 2023

Bone Joint Res

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AimsLumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease.MethodsWe conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes.ResultsTWAS identified 295 genes with permutation p-values < 0.05 for skeletal muscle and 79 genes associated for the whole blood, such as RCHY1 (PTWAS = 0.001). Those genes were enriched in 112 gene ontology (GO) terms and five Kyoto Encyclopedia of Genes and Genomes pathways, such as ‘chemical carcinogenesis - reactive oxygen species’ (LogP value = −2.139). Further comparing the TWAS significant genes with the differentially expressed genes identified by mRNA expression profiles of LSS found 18 overlapped genes, such as interleukin 15 receptor subunit alpha (IL15RA) (PTWAS = 0.040, PmRNA = 0.010). Moreover, 71 common GO terms were detected for the enrichment results of TWAS and mRNA expression profiles, such as negative regulation of cell differentiation (LogP value = −2.811).ConclusionThis study revealed the genetic mechanism behind the pathological changes in LSS, and may provide novel insights for the early diagnosis and intervention of LSS.Cite this article: Bone Joint Res 2023;12(6):387–396.

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“… 412 IL-15 has been reported to have local effects on skeletal muscles, such as promoting myoblast differentiation. 413 , 414 Furthermore, exercise-mediated improvements in the healing of aged skin depend upon circulating IL-15. Exercise-mimicking recombinant IL-15 directly enhanced the growth of the aged mouse fibroblasts and keratinocytes, promoting impaired wound healing via activation of signal transducer and activator of transcription 3 signaling pathway, even though it was barely scarless regeneration 415 (Fig.…”

Section: Potential Exercise Mimetics Contributing To Tissue Regenerationmentioning

confidence: 99%

Molecular mechanisms of exercise contributing to tissue regeneration

Chen

Zhou

et al. 2022

Sig Transduct Target Ther

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Physical activity has been known as an essential element to promote human health for centuries. Thus, exercise intervention is encouraged to battle against sedentary lifestyle. Recent rapid advances in molecular biotechnology have demonstrated that both endurance and resistance exercise training, two traditional types of exercise, trigger a series of physiological responses, unraveling the mechanisms of exercise regulating on the human body. Therefore, exercise has been expected as a candidate approach of alleviating a wide range of diseases, such as metabolic diseases, neurodegenerative disorders, tumors, and cardiovascular diseases. In particular, the capacity of exercise to promote tissue regeneration has attracted the attention of many researchers in recent decades. Since most adult human organs have a weak regenerative capacity, it is currently a key challenge in regenerative medicine to improve the efficiency of tissue regeneration. As research progresses, exercise-induced tissue regeneration seems to provide a novel approach for fighting against injury or senescence, establishing strong theoretical basis for more and more “exercise mimetics.” These drugs are acting as the pharmaceutical alternatives of those individuals who cannot experience the benefits of exercise. Here, we comprehensively provide a description of the benefits of exercise on tissue regeneration in diverse organs, mainly focusing on musculoskeletal system, cardiovascular system, and nervous system. We also discuss the underlying molecular mechanisms associated with the regenerative effects of exercise and emerging therapeutic exercise mimetics for regeneration, as well as the associated opportunities and challenges. We aim to describe an integrated perspective on the current advances of distinct physiological mechanisms associated with exercise-induced tissue regeneration on various organs and facilitate the development of drugs that mimics the benefits of exercise.

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Interleukin‐15 receptor subunit alpha regulates interleukin‐15 localization and protein expression in skeletal muscle cells

Cited by 7 publications

References 44 publications

Preoperative inflammatory biomarkers reveal renal involvement in postsurgical mortality in hip fracture patients: an exploratory study

Preoperative inflammatory biomarkers reveal renal involvement in postsurgical mortality in hip fracture patients: an exploratory study

Transcriptome-wide association study reveals candidate causal genes for lumbar spinal stenosis

Molecular mechanisms of exercise contributing to tissue regeneration

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