Involvement of adiponectin in age-related increases in tear production in mice

Involvement of adiponectin in age-related increases in tear production in mice
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DOI:
10.18632/aging.102322
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发表时间:
2019-10-15
期刊:
影响因子:
5.2
通讯作者:
Matsushita, Kenji
Matsushita, Kenji
中科院分区:
医学2区
文献类型:
--
作者:
Shikama, Yosuke;Kurosawa, Mie;Matsushita, Kenji

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人类眼睛中常见的年龄相关变化有助于干眼症的发展,包括水性泪液产生的减少。尽管淋巴细胞浸润到泪腺中会随着年龄的增长而发生,但在小鼠中也观察到与年龄相关的泪液分泌增加;然而,这种增加的机制仍不清楚。我们在此证明,泪液产生的增加不依赖于体重增加或全身条件,如胰岛素抵抗,使用老年小鼠和高脂肪饮食喂养的小鼠。所获得的结果还表明,衰老相关的T(SA-T)细胞在老年小鼠,特别是雌性小鼠的泪腺中积累。核转录因子过氧化物酶体增殖物激活受体-γ(过氧化物酶体增殖物激活受体γ)在整个泪腺和泪腺上皮细胞分离的表达水平显着高于老年小鼠比年轻小鼠。脂联素及其受体之一AdipoR 2的表达水平在老年小鼠的泪腺中也有所增加,但在高脂饮食喂养的小鼠中则没有。总的来说,目前的结果表明,PPAR。和脂联素介导的信号传导有助于小鼠泪液产生的年龄相关性增加,并且具有作为治疗人类干眼的治疗靶点的潜力。
Common age-related changes in the human eye contribute to the development of dry eye, including decreases in aqueous tear production. Although the infiltration of lymphocytes into the lacrimal glands occurs with age, age-related increases in tear production have also been observed in mice; however, the mechanisms underlying this increase remain unclear. We herein demonstrated that increases in tear production were not dependent on body weight gain or systemic conditions, such as insulin resistance, using aged mice and high-fat diet-fed mice. The results obtained also showed that senescence-associated T (SA-T) cells accumulated in the lacrimal glands of aged mice, particularly females. Expression levels of the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPAR gamma) in whole lacrimal glands and epithelial cells isolated from lacrimal glands were significantly higher in aged mice than in young mice. The expression levels of adiponectin and one of its receptors, AdipoR2, also increased in the lacrimal glands of aged mice, but not in those of high-fat diet-fed mice. Collectively, the present results indicate that PPAR. and adiponectin-mediated signaling contribute to age-related increases in tear production in mice and have potential as therapeutic targets for the treatment of dry eye in humans.