Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/75284
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Johno, H. | - |
dc.contributor.author | Nakajima, S. | - |
dc.contributor.author | Kato, H. | - |
dc.contributor.author | Yao, J. | - |
dc.contributor.author | Paton, A. | - |
dc.contributor.author | Paton, J. | - |
dc.contributor.author | Katoh, R. | - |
dc.contributor.author | Shimizu, F. | - |
dc.contributor.author | Kitamura, M. | - |
dc.date.issued | 2012 | - |
dc.identifier.citation | American Journal of Pathology, 2012; 181(6):1977-1990 | - |
dc.identifier.issn | 0002-9440 | - |
dc.identifier.issn | 1525-2191 | - |
dc.identifier.uri | http://hdl.handle.net/2440/75284 | - |
dc.description.abstract | During recovery from acute glomerulonephritis, cell proliferation, matrix expansion, and expression of the dedifferentiation marker α-smooth muscle actin (α-SMA) subside spontaneously. However, the molecular mechanisms underlying this recovery process remain elusive. In mesangioproliferative glomerulonephritis, the unfolded protein response (UPR) is induced in activated, dedifferentiated mesangial cells. We investigated the role of the UPR in mesangial cell deactivation and redifferentiation and found that, during experimental glomerulonephritis in rats, reinforcement of the UPR significantly attenuated mesangial cell proliferation, matrix expansion, and expression of α-SMA. Consistent with this in vivo result, induction of the UPR suppressed cell proliferation and transcriptional expression of type IV collagen (ColIV) and α-SMA in activated mesangial cells. The UPR reduced phosphorylation of Akt in vitro and in vivo, and it was responsible for attenuation of cell proliferation. The UPR also preferentially depressed levels of total and phosphorylated Smads without affecting transcriptional levels, and it was responsible for suppression of ColIV and α-SMA. Translational suppression via the eIF2α pathway, but not proteasome-mediated protein degradation, was responsible for the down-regulation of Smads. These results suggest the novel potential of the UPR to facilitate a phenotypic shift of activated glomerular cells toward deactivation and redifferentiation. The UPR may serve as endogenous machinery that supports recovery of glomeruli from acute inflammation. | - |
dc.description.statementofresponsibility | Hisashi Johno, Shotaro Nakajima, Hironori Kato, Jian Yao, Adrienne W. Paton, James C. Paton, Ryohei Katoh, Fujio Shimizu, and Masanori Kitamura | - |
dc.language.iso | en | - |
dc.publisher | Amer Soc Investigative Pathology Inc | - |
dc.rights | Copyright © 2012 American Society for Investigative Pathology | - |
dc.source.uri | http://dx.doi.org/10.1016/j.ajpath.2012.08.015 | - |
dc.subject | Kidney Glomerulus | - |
dc.subject | Cell Line | - |
dc.subject | Animals | - |
dc.subject | Rats | - |
dc.subject | Rats, Sprague-Dawley | - |
dc.subject | Inflammation | - |
dc.subject | Actins | - |
dc.subject | Eukaryotic Initiation Factor-2 | - |
dc.subject | Collagen Type IV | - |
dc.subject | Signal Transduction | - |
dc.subject | Cell Differentiation | - |
dc.subject | Cell Proliferation | - |
dc.subject | Transcription, Genetic | - |
dc.subject | Phenotype | - |
dc.subject | Models, Biological | - |
dc.subject | Male | - |
dc.subject | Proto-Oncogene Proteins c-akt | - |
dc.subject | Smad Proteins | - |
dc.subject | Unfolded Protein Response | - |
dc.title | Unfolded protein response causes a phenotypic shift of inflamed glomerular cells toward redifferentiation through dual blockade of Akt and Smad signaling pathways | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1016/j.ajpath.2012.08.015 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Paton, J. [0000-0001-9807-5278] | - |
Appears in Collections: | Aurora harvest 4 Molecular and Biomedical Science publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.