| TGF-{beta}1 protects against mesangial cell apoptosis via induction of autophagy. | |
| | |
MedLine Citation:
|
PMID: 20876581 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Autophagy can lead to cell death in response to stress, but it can also act as a protective mechanism for cell survival. We show that TGF-β1 induces autophagy and protects glomerular mesangial cells from undergoing apoptosis during serum deprivation. Serum withdrawal rapidly induced autophagy within 1 h in mouse mesangial cells (MMC) as determined by increased microtubule-associated protein 1 light chain 3 (LC3) levels and punctate distribution of the autophagic vesicle-associated-form LC3-II. We demonstrate that after 1 h there was a time-dependent decrease in LC3 levels that was accompanied by induction of apoptosis, evidenced by increases in cleaved caspase 3. However, treatment with TGF-β1 resulted in induction of the autophagy protein LC3 while suppressing caspase 3 activation. TGF-β1 failed to rescue MMC from serum deprivation-induced apoptosis upon knockdown of LC3 by siRNA and in MMC from LC3 null (LC3(-/-)) mice. We show that TGF-β1 induced autophagy through TAK1 and Akt activation, and inhibition of PI3K-Akt pathway by LY294002 or dominant-negative Akt suppressed LC3 levels and enhanced caspase 3 activation. TGF-β1 also up-regulated cyclin D1 and E protein levels while down-regulating p27, thus stimulating cell cycle progression. Bafilomycin A1, but not MG132, blocked TGF-β1 down-regulation of p27, suggesting that p27 levels were regulated through autophagy. Taken together, our data indicate that TGF-β1 rescues MMC from serum deprivation-induced apoptosis via induction of autophagy through activation of the Akt pathway. The autophagic process may constitute an adaptive mechanism to glomerular injury by inhibiting apoptosis and promoting mesangial cell survival. |
| | |
Authors:
|
Yan Ding; Jin Kuk Kim; Sung Il Kim; Hee-Jun Na; Soo Young Jun; Seon Jin Lee; Mary E Choi |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-09-28 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Nov |
Date Detail:
|
Created Date: 2010-11-24 Completed Date: 2010-12-30 Revised Date: 2011-12-21 |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
|
Languages: eng Pagination: 37909-19 Citation Subset: IM |
Affiliation:
|
Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Apoptosis* Autophagy* Caspase 3 / genetics, metabolism Cells, Cultured Male Mesangial Cells / cytology*, metabolism Mice Mice, Inbred C57BL Mice, Knockout Microtubule-Associated Proteins / genetics, metabolism Transforming Growth Factor beta1 / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
R01 DK57661/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/MAP1LC3 protein, mouse; 0/Microtubule-Associated Proteins; 0/Transforming Growth Factor beta1; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Regulation of ghrelin signaling by a leptin-induced gene, negative regulatory element-binding protei...
Next Document: Poly(ADP-ribose) polymerase-1 (PARP-1) contributes to the barrier function of a vertebrate chromatin...