IL-6-STAT3 signaling and premature senescence

Kojima, Hiroyuki; Inoue, Toshiaki; Kunimoto, Hiroyuki; Nakajima, Kōichi

doi:10.4161/jkst.25763

Cited by 129 publications

(114 citation statements)

References 87 publications

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“…Aging‐related increase in levels of circulatory IL‐6 has been previously reported in humans and mice, and IL‐6 has been proposed as one of the factors contributing to age‐related decline in organism function (Washington et al ., 2011). The role of IL‐6 in cellular senescence has also been demonstrated (Kojima et al ., 2013). It remains to be established whether the effects of IL‐6 on miR‐143:Igfbp5 interactions are maintained in vivo and whether these indeed contribute to defective muscle regeneration during aging.…”

Section: Discussionmentioning

confidence: 99%

Age‐related changes in miR‐143‐3p:Igfbp5 interactions affect muscle regeneration

et al. 2016

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SummaryA common characteristic of aging is defective regeneration of skeletal muscle. The molecular pathways underlying age‐related decline in muscle regenerative potential remain elusive. microRNAs are novel gene regulators controlling development and homeostasis and the regeneration of most tissues, including skeletal muscle. Here, we use satellite cells and primary myoblasts from mice and humans and an in vitro regeneration model, to show that disrupted expression of microRNA‐143‐3p and its target gene, Igfbp5, plays an important role in muscle regeneration in vitro. We identified miR‐143 as a regulator of the insulin growth factor‐binding protein 5 (Igfbp5) in primary myoblasts and show that the expression of miR‐143 and its target gene is disrupted in satellite cells from old mice. Moreover, we show that downregulation of miR‐143 during aging may act as a compensatory mechanism aiming at improving myogenesis efficiency; however, concomitant upregulation of miR‐143 target gene, Igfbp5, is associated with increased cell senescence, thus affecting myogenesis. Our data demonstrate that dysregulation of miR‐143‐3p:Igfbp5 interactions in satellite cells with age may be responsible for age‐related changes in satellite cell function.

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Section: Discussionmentioning

confidence: 99%

Age‐related changes in miR‐143‐3p:Igfbp5 interactions affect muscle regeneration

et al. 2016

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“…IL-6 acts on cells as a dimer by binding to a specific IL-6 receptor (IL-6R) complex composed of two IL-6Rα chains (also known as IL-6Rα, gp80 or CD126) and the resultant IL-6/IL-6Rα complex associates with two signal-generating receptor beta chain subunits, named gp130 (also known as IL-6Rβ or CD130), at three distinct receptor-binding sites (Kojima et al 2013). In contrast to gp130, IL-6Rα is only expressed on a limited number of cell types, which actually facilitates the selective activation of several target cells .…”

Section: Biology and Functions Of Il-6mentioning

confidence: 99%

Programmed cell senescence: role of IL-6 in the pituitary

Sapochnik

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2017

Journal of Molecular Endocrinology

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IL-6 is a pleiotropic cytokine with multiple pathophysiological functions. As a key factor of the senescence secretome, it can not only promote tumorigenesis and cell proliferation but also exert tumor suppressive functions, depending on the cellular context. IL-6, as do other cytokines, plays important roles in the function, growth and neuroendocrine responses of the anterior pituitary gland. The multiple actions of IL-6 on normal and adenomatous pituitary function, cell proliferation, angiogenesis and extracellular matrix remodeling indicate its importance in the regulation of the anterior pituitary. Pituitary tumors are mostly benign adenomas with low mitotic index and rarely became malignant. Premature senescence occurs in slow-growing benign tumors, like pituitary adenomas. The dual role of IL-6 in senescence and tumorigenesis is well represented in pituitary tumor development, as it has been demonstrated that effects of paracrine IL-6 may allow initial pituitary cell growth, whereas autocrine IL-6 in the same tumor triggers senescence and restrains aggressive growth and malignant transformation. IL-6 is instrumental in promotion and maintenance of the senescence program in pituitary adenomas.

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“…IL-6 production has previously been linked to stressinduced premature senescence (SIPS)/replicative senescence and the senescence-associated secretory phenotype (SASP). 48,49 A recent study by Lagerge and colleagues indicated that mTOR inhibition with rapamycin or knockdown of mTOR components causes decreased IL-6/cytokine production in senescent fibroblasts. 50 Although we observed the opposite effect, with increased IL-6 and IL-8 production, our system used proliferating Figure 5.…”

Section: Genesetmentioning

confidence: 99%