Inhibition of mTORC1 signaling protects kidney from irradiation-induced toxicity via accelerating recovery of renal stem-like cells

Shao, Longquan; Yang, Wuping; Xu, Rui; Zhu, Shuqin; Huang, Yanqiu; Li, Huan; Wu, Xincheng; Yue, Mengzhen; Xiong, Xin; Chen, Xiaowen; Kuang, Bohai; Fan, Guang; Zhu, Qing; Zeng, Huihong

doi:10.1186/s13287-018-0963-5

Cited by 10 publications

(4 citation statements)

References 48 publications

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“…Radioprotection of rapamycin on normal tissues is also supported by a recent study, showing that rapamycin treatment prevented irradiation-induced salivary hypofunction in swine and human submandibular gland HSG cells (Zhu et al., 2016). Recent data from our lab have shown that rapamycin treatment after irradiation protected kidneys in mice by inhibiting cellular apoptosis (Shao et al., 2018). However, the effects of rapamycin treatment on liver and kidney before irradiation remain warranted in our future investigation.…”

Section: Discussionmentioning

confidence: 99%

Transient Inhibition of mTORC1 Signaling Ameliorates Irradiation-Induced Liver Damage

et al. 2019

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Recurrent liver cancer after surgery is often treated with radiotherapy, which induces liver damage. It has been documented that activation of the TGF-β and NF-κB signaling pathways plays important roles in irradiation-induced liver pathologies. However, the significance of mTOR signaling remains undefined after irradiation exposure. In the present study, we investigated the effects of inhibiting mTORC1 signaling on irradiated livers. Male C57BL/6J mice were acutely exposed to 8.0 Gy of X-ray total body irradiation and subsequently treated with rapamycin. The effects of rapamycin treatment on irradiated livers were examined at days 1, 3, and 7 after exposure. The results showed that 8.0 Gy of irradiation resulted in hepatocyte edema, hemorrhage, and sinusoidal congestion along with a decrease of ALB expression. Exposure of mice to irradiation significantly activated the mTORC1 signaling pathway determined by pS6 and p-mTOR expression via western blot and immunostaining. Transient inhibition of mTORC1 signaling by rapamycin treatment consistently accelerated liver recovery from irradiation, which was evidenced by decreasing sinusoidal congestion and increasing ALB expression after irradiation. The protective role of rapamycin on irradiated livers might be mediated by decreasing cellular apoptosis and increasing autophagy. These data suggest that transient inhibition of mTORC1 signaling by rapamycin protects livers against irradiation-induced damage.

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Section: Discussionmentioning

confidence: 99%

Transient Inhibition of mTORC1 Signaling Ameliorates Irradiation-Induced Liver Damage

et al. 2019

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“…Rapamycin administration efficiently ameliorated radiation-induced testicular damage. In our previous studies, we have shown that radiation can over-activate the mTORC1 pathway in liver and kidney, leading to acute liver and kidney damage ( Shao et al, 2018 ; Yang et al, 2019 ). When exploring the relationship between the level of oxidative stress and mTORC1 of adult stem cells including SSCs, researchers found that rapamycin can inhibit mTORC1 to alleviate the senescence of SSCs induced by oxidative stress and promote the self-renewal and proliferation of SSCs ( Kofman et al, 2012 ), which is consistent with our finding that rapamycin can alleviate testicular damage caused by radiation.…”

Section: Discussionmentioning

confidence: 99%

Rapamycin Ameliorates Radiation-Induced Testis Damage in Mice

Yang

Luan

et al. 2022

Front. Cell Dev. Biol.

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Male infertility is an important problem in human and animal reproduction. The testis is the core of male reproduction, which is very sensitive to radiation. The decline of male reproductive ability is a common trend in the world. Radiation is a physical factor leading to abnormal male reproductive function. To investigate the potential mechanisms of testicular damage induced by radiation and explore effective strategies to alleviate radiation-induced testis injury, C57BL/6 mice were irradiated with 8.0 Gy of X-ray irradiation. Testis and epididymis were collected at days 1, 3, and 7 after radiation exposure to analyze spermatogonia and sperm function. The results showed that radiation significantly destroyed testicular structure and reduced the numbers of spermatogonia. These were associated with mTORC1 signaling activation, decreased cellular proliferation and increased apoptotic cells in the irradiated testis. Rapamycin significantly blocked mTORC1 signaling pathway in the irradiated testis. Inhibition of mTORC1 signaling pathway by rapamycin treatment after radiation could significantly improve cell proliferation in testis and alleviate radiation-induced testicular injury after radiation exposure. Rapamycin treatment benefited cell survival in testis to maintain spermatogenesis cycle at 35 days after irradiation. These findings imply that rapamycin treatment can accelerate testis recovery under radiation condition through inhibiting mTORC1 signaling pathway.

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“…Some studies have described a crucial involvement of autophagy in radiation-induced regeneration of SGs [ 94 , 99 ], intestine [ 95 , 100 ], and kidney [ 101 ] ( Figure 2 h). Morgan-Bathke et al [ 94 ] explored the role of autophagy in parotid gland IR-triggered repair of acinar cells ( Figure 2 h), a population that is known to self-duplicate to contribute to endogenous regeneration [ 22 ].…”

Section: Signaling Pathways That Contribute To Sc Radiation Responmentioning

confidence: 99%

“…On the other hand, the use of the autophagy inhibitor chloroquine did not rescue the saliva production. Similarly, the administration of Rapamycin induced renal protection against radiation damage ( Figure 2 h) [ 101 ]. Kidneys of mice exposed to 8 Gy of total body IR showed a reduced expression of the renal SC marker CD133, activation of mTORC1 signaling, and inhibition of autophagy, while rapamycin treatment ameliorated renal morphological damage, increased CD133 expression, reduced apoptosis, and inhibited the overactivation of TGF-β and NF-κB.…”

Section: Signaling Pathways That Contribute To Sc Radiation Responmentioning

confidence: 99%

The Radiation-Induced Regenerative Response of Adult Tissue-Specific Stem Cells: Models and Signaling Pathways

Martinez

Giuranno

Vooijs

et al. 2021

Cancers

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Radiotherapy is involved in the treatment of many cancers, but damage induced to the surrounding normal tissue is often inevitable. Evidence suggests that the maintenance of homeostasis and regeneration of the normal tissue is driven by specific adult tissue stem/progenitor cells. These tasks involve the input from several signaling pathways. Irradiation also targets these stem/progenitor cells, triggering a cellular response aimed at achieving tissue regeneration. Here we discuss the currently used in vitro and in vivo models and the involved specific tissue stem/progenitor cell signaling pathways to study the response to irradiation. The combination of the use of complex in vitro models that offer high in vivo resemblance and lineage tracing models, which address organ complexity constitute potential tools for the study of the stem/progenitor cellular response post-irradiation. The Notch, Wnt, Hippo, Hedgehog, and autophagy signaling pathways have been found as crucial for driving stem/progenitor radiation-induced tissue regeneration. We review how these signaling pathways drive the response of solid tissue-specific stem/progenitor cells to radiotherapy and the used models to address this

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Inhibition of mTORC1 signaling protects kidney from irradiation-induced toxicity via accelerating recovery of renal stem-like cells

Cited by 10 publications

References 48 publications

Transient Inhibition of mTORC1 Signaling Ameliorates Irradiation-Induced Liver Damage

Transient Inhibition of mTORC1 Signaling Ameliorates Irradiation-Induced Liver Damage

Rapamycin Ameliorates Radiation-Induced Testis Damage in Mice

The Radiation-Induced Regenerative Response of Adult Tissue-Specific Stem Cells: Models and Signaling Pathways

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