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Cited by 234

The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

Rtp801, a suppressor of mTOR signaling, is an essential mediator of cigarette smoke–induced pulmonary injury and emphysema

Open access
Yoshida, Toshinori, Mett, Igor, Bhunia, Anil K, Bowman, Joel, Perez, Mario, Zhang, Li, Gandjeva, Aneta, Zhen, Lijie, Chukwueke, Ugonma, Mao, Tianzhi, Richter, Amy, Brown, Emile, Ashush, Hagit, Notkin, Natalie, Gelfand, Anna, Thimmulappa, Rajesh K, Rangasamy, Tirumalai, Sussan, Thomas, Cosgrove, Gregory, Mouded, Majd, Shapiro, Steven D, Petrache, Irina, Biswal, Shyam, Feinstein, Elena, Tuder, Rubin M·2010·Nature Medicine
DOI 10.1038/nm.2157
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Abstract

Rtp801 (also known as Redd1, and encoded by Ddit4), a stress-related protein triggered by adverse environmental conditions, inhibits mammalian target of rapamycin (mTOR) by stabilizing the TSC1-TSC2 inhibitory complex and enhances oxidative stress–dependent cell death. We postulated that Rtp801 acts as a potential amplifying switch in the development of cigarette smoke–induced lung injury, leading to emphysema. Rtp801 mRNA and protein were overexpressed in human emphysematous lungs and in lungs of mice exposed to cigarette smoke. The regulation of Rtp801 expression by cigarette smoke may rely on oxidative stress–dependent activation of the CCAAT response element in its promoter. We also found that Rtp801 was necessary and sufficient for nuclear factor-κB (NF-κB) activation in cultured cells and, when forcefully expressed in mouse lungs, it promoted NF-κB activation, alveolar inflammation, oxidative stress and apoptosis of alveolar septal cells. In contrast, Rtp801 knockout mice were markedly protected against acute cigarette smoke–induced lung injury, partly via increased mTOR signaling, and, when exposed chronically to cigarette smoke, against emphysema. Our data support the notion that Rtp801 may represent a major molecular sensor and mediator of cigarette smoke–induced lung injury.

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Metadata

Authors
Yoshida, T., Mett, I., Bhunia, A. K., Bowman, J., Perez, M., Zhang, L., Gandjeva, A., Zhen, L., Chukwueke, U., Mao, T., Richter, A., Brown, E., Ashush, H., Notkin, N., Gelfand, A., Thimmulappa, R. K., Rangasamy, T., Sussan, T., Cosgrove, G., Mouded, M., Shapiro, S. D., Petrache, I., Biswal, S., Feinstein, E., & Tuder, R. M.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2010-05-16
Volume
16
Issue
7
Pages
767-773
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm.2157
OpenAlex
W2120372473
Cited by
234
References
5
FWCI
12.54
Type
journal article
Language
en
Open access
green

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