Show simple item record

dc.contributor.authorSundaresan, NR
dc.contributor.authorBindu, S
dc.contributor.authorPillai, VB
dc.contributor.authorSamant, S
dc.contributor.authorPan, Y
dc.contributor.authorHuang, JY
dc.contributor.authorGupta, M
dc.contributor.authorNagalingam, RS
dc.contributor.authorWolfgeher, D
dc.contributor.authorVerdin, E
dc.contributor.authorGupta, MP
dc.date.accessioned2016-05-10T15:08:00Z
dc.date.available2016-05-10T15:08:00Z
dc.date.issued2015-12-14
dc.identifier.bibliographicCitationSundaresan, N. R., Bindu, S., Pillai, V. B., Samant, S., Pan, Y., Huang, J. Y., Gupta, M., Nagalingam, R. S., Wolfgeher, D., Verdin, E. and Gupta, M. P. SIRT3 Blocks Aging-Associated Tissue Fibrosis in Mice by Deacetylating and Activating Glycogen Synthase Kinase 3 beta. Molecular and Cellular Biology. 2016. 36(5): 678-692. DOI: 10.1128/mcb.00586-15.en_US
dc.identifier.issn0270-7306
dc.identifier.urihttp://hdl.handle.net/10027/20553
dc.descriptionThis is a copy of an article published in Molecular and Cellular Biology © 2015 American Society for Microbiology Publications.en_US
dc.description.abstractTissue fibrosis is a major cause of organ dysfunction during chronic diseases and aging. A critical step in this process is transforming growth factor 1 (TGF-1)-mediated transformation of fibroblasts into myofibroblasts, cells capable of synthesizing extracellular matrix. Here, we show that SIRT3 controls transformation of fibroblasts into myofibroblasts via suppressing the profibrotic TGF-1 signaling. We found that Sirt3 knockout (KO) mice with age develop tissue fibrosis of multiple organs, including heart, liver, kidney, and lungs but not whole-body SIRT3-overexpressing mice. SIRT3 deficiency caused induction of TGF-1 expression and hyperacetylation of glycogen synthase kinase 3 (GSK3) at residue K15, which negatively regulated GSK3 activity to phosphorylate the substrates Smad3 and -catenin. Reduced phosphorylation led to stabilization and activation of these transcription factors regulating expression of the profibrotic genes. SIRT3 deacetylated and activated GSK3 and thereby blocked TGF-1 signaling and tissue fibrosis. These data reveal a new role of SIRT3 to negatively regulate aging-associated tissue fibrosis and discloses a novel phosphorylation-independent mechanism controlling the catalytic activity of GSK3. Fibrosis.en_US
dc.description.sponsorshipThis study was supported by: HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) provided funding to Mahesh P. Gupta under grant number RO1 HL117041. HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) provided funding to Mahesh P. Gupta under grant number RO1 HL111455en_US
dc.publisherAmerican Society for Microbiologyen_US
dc.titleSIRT3 Blocks Aging-Associated Tissue Fibrosis in Mice by Deacetylating and Activating Glycogen Synthase Kinase 3β.en_US
dc.typeArticleen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record