F4/80+ macrophages contribute to clearance of senescent cells in the mouse postpartum uterus

Mahiro Egashira, Yasushi Hirota, Ryoko Shimizu, Tomoko Saito-Fujita, Hirofumi Haraguchi, Leona Matsumoto, Mitsunori Matsuo, Takehiro Hiraoka, Tomoki Tanaka, Shun Akaeda, Chiaki Takehisa, Mayuko Saito-Kanatani, Kei Ichiro Maeda, Tomoyuki Fujii, Yutaka Osuga

Research output: Contribution to journalArticle

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Abstract

Cellular senescence, defined as an irreversible cell cycle arrest, exacerbates the tissue microenvironment. Our previous study demonstrated that mouse uterine senescent cells were physiologically increased according to gestational days and that their abnormal accumulation was linked to the onset of preterm delivery.Wehypothesized that there is a mechanism for removal of senescent cells after parturition to maintain uterine function. In the current study, we noted abundant uterine senescent cells and their gradual disappearance in wild-type postpartum mice. F4/80+ macrophages were present specifically around the area rich in senescent cells. Depletion of macrophages in the postpartum mice using anti-F4/80 antibody enlarged the area of senescent cells in the uterus. We also found excessive uterine senescent cells and decreased second pregnancy success rate in a preterm birth model using uterine p53-deleted mice. Furthermore, a decrease in F4/80+ cells and an increase in CD11b+ cells with a senescence-associated inflammatory microenvironment were observed in the p53-deleted uterus, suggesting that uterine p53 deficiency affects distribution of the macrophage subpopulation, interferes with senescence clearance, and promotes senescenceinduced inflammation. These findings indicate that the macrophage is a key player in the clearance of uterine senescent cells to maintain postpartum uterine function.

Original languageEnglish
Pages (from-to)2344-2353
Number of pages10
JournalEndocrinology
Volume158
Issue number7
DOIs
Publication statusPublished - 2017 Jul 1

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Postpartum Period
Uterus
Macrophages
Cell Aging
Premature Birth
Pregnancy Rate
Cell Cycle Checkpoints
Parturition
Inflammation
Antibodies

ASJC Scopus subject areas

  • Endocrinology

Cite this

Egashira, M., Hirota, Y., Shimizu, R., Saito-Fujita, T., Haraguchi, H., Matsumoto, L., ... Osuga, Y. (2017). F4/80+ macrophages contribute to clearance of senescent cells in the mouse postpartum uterus. Endocrinology, 158(7), 2344-2353. https://doi.org/10.1210/en.2016-1886

F4/80+ macrophages contribute to clearance of senescent cells in the mouse postpartum uterus. / Egashira, Mahiro; Hirota, Yasushi; Shimizu, Ryoko; Saito-Fujita, Tomoko; Haraguchi, Hirofumi; Matsumoto, Leona; Matsuo, Mitsunori; Hiraoka, Takehiro; Tanaka, Tomoki; Akaeda, Shun; Takehisa, Chiaki; Saito-Kanatani, Mayuko; Maeda, Kei Ichiro; Fujii, Tomoyuki; Osuga, Yutaka.

In: Endocrinology, Vol. 158, No. 7, 01.07.2017, p. 2344-2353.

Research output: Contribution to journalArticle

Egashira, M, Hirota, Y, Shimizu, R, Saito-Fujita, T, Haraguchi, H, Matsumoto, L, Matsuo, M, Hiraoka, T, Tanaka, T, Akaeda, S, Takehisa, C, Saito-Kanatani, M, Maeda, KI, Fujii, T & Osuga, Y 2017, 'F4/80+ macrophages contribute to clearance of senescent cells in the mouse postpartum uterus', Endocrinology, vol. 158, no. 7, pp. 2344-2353. https://doi.org/10.1210/en.2016-1886
Egashira M, Hirota Y, Shimizu R, Saito-Fujita T, Haraguchi H, Matsumoto L et al. F4/80+ macrophages contribute to clearance of senescent cells in the mouse postpartum uterus. Endocrinology. 2017 Jul 1;158(7):2344-2353. https://doi.org/10.1210/en.2016-1886
Egashira, Mahiro ; Hirota, Yasushi ; Shimizu, Ryoko ; Saito-Fujita, Tomoko ; Haraguchi, Hirofumi ; Matsumoto, Leona ; Matsuo, Mitsunori ; Hiraoka, Takehiro ; Tanaka, Tomoki ; Akaeda, Shun ; Takehisa, Chiaki ; Saito-Kanatani, Mayuko ; Maeda, Kei Ichiro ; Fujii, Tomoyuki ; Osuga, Yutaka. / F4/80+ macrophages contribute to clearance of senescent cells in the mouse postpartum uterus. In: Endocrinology. 2017 ; Vol. 158, No. 7. pp. 2344-2353.
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