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- Publisher Website: 10.1038/s41467-018-04994-z
- Scopus: eid_2-s2.0-85049396675
- PMID: 29967491
- WOS: WOS:000436958500007
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Article: TGF-β signaling alters H4K20me3 status via miR-29 and contributes to cellular senescence and cardiac aging
Title | TGF-β signaling alters H4K20me3 status via miR-29 and contributes to cellular senescence and cardiac aging |
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Authors | |
Keywords | adult animal experiment cell aging cell disruption chromatin immunoprecipitation |
Issue Date | 2018 |
Publisher | Nature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html |
Citation | Nature Communications, 2018, v. 9 n. 1, p. article no. 2560 How to Cite? |
Abstract | Cellular senescence is a well-orchestrated programmed process involved in age-related pathologies, tumor suppression and embryonic development. TGF-β/Smad is one of the predominant pathways that regulate damage-induced and developmentally programmed senescence. Here we show that canonical TGF-β signaling promotes senescence via miR-29-induced loss of H4K20me3. Mechanistically, oxidative stress triggers TGF-β signaling. Activated TGF-β signaling gives rise to acute accumulation of miR-29a and miR-29c, both of which directly suppress their novel target, Suv4-20h, thus reducing H4K20me3 abundance in a Smad-dependent manner, which compromises DNA damage repair and genome maintenance. Loss of H4K20me3 mediated by the senescent TGF-β/miR-29 pathway contributes to cardiac aging in vivo. Disruption of TGF-β signaling restores H4K20me3 and improves cardiac function in aged mice. Our study highlights the sequential mechanisms underlying the regulation of senescence, from senescence-inducing triggers to activation of responsive signaling followed by specific epigenetic alterations, shedding light on potential therapeutic interventions in cardiac aging. |
Persistent Identifier | http://hdl.handle.net/10722/277181 |
ISSN | 2023 Impact Factor: 14.7 2023 SCImago Journal Rankings: 4.887 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Lyu, G | - |
dc.contributor.author | Guan, Y | - |
dc.contributor.author | Zhang, C | - |
dc.contributor.author | Zong, L | - |
dc.contributor.author | Sun, L | - |
dc.contributor.author | Huang, X | - |
dc.contributor.author | Huang, L | - |
dc.contributor.author | Zhang, L | - |
dc.contributor.author | Tian, XL | - |
dc.contributor.author | Zhou, Z | - |
dc.contributor.author | Tao, W | - |
dc.date.accessioned | 2019-09-20T08:46:09Z | - |
dc.date.available | 2019-09-20T08:46:09Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | Nature Communications, 2018, v. 9 n. 1, p. article no. 2560 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | http://hdl.handle.net/10722/277181 | - |
dc.description.abstract | Cellular senescence is a well-orchestrated programmed process involved in age-related pathologies, tumor suppression and embryonic development. TGF-β/Smad is one of the predominant pathways that regulate damage-induced and developmentally programmed senescence. Here we show that canonical TGF-β signaling promotes senescence via miR-29-induced loss of H4K20me3. Mechanistically, oxidative stress triggers TGF-β signaling. Activated TGF-β signaling gives rise to acute accumulation of miR-29a and miR-29c, both of which directly suppress their novel target, Suv4-20h, thus reducing H4K20me3 abundance in a Smad-dependent manner, which compromises DNA damage repair and genome maintenance. Loss of H4K20me3 mediated by the senescent TGF-β/miR-29 pathway contributes to cardiac aging in vivo. Disruption of TGF-β signaling restores H4K20me3 and improves cardiac function in aged mice. Our study highlights the sequential mechanisms underlying the regulation of senescence, from senescence-inducing triggers to activation of responsive signaling followed by specific epigenetic alterations, shedding light on potential therapeutic interventions in cardiac aging. | - |
dc.language | eng | - |
dc.publisher | Nature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html | - |
dc.relation.ispartof | Nature Communications | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | adult | - |
dc.subject | animal experiment | - |
dc.subject | cell aging | - |
dc.subject | cell disruption | - |
dc.subject | chromatin immunoprecipitation | - |
dc.title | TGF-β signaling alters H4K20me3 status via miR-29 and contributes to cellular senescence and cardiac aging | - |
dc.type | Article | - |
dc.identifier.email | Zhou, Z: zhongjun@hku.hk | - |
dc.identifier.authority | Zhou, Z=rp00503 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1038/s41467-018-04994-z | - |
dc.identifier.pmid | 29967491 | - |
dc.identifier.pmcid | PMC6028646 | - |
dc.identifier.scopus | eid_2-s2.0-85049396675 | - |
dc.identifier.hkuros | 305499 | - |
dc.identifier.volume | 9 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | article no. 2560 | - |
dc.identifier.epage | article no. 2560 | - |
dc.identifier.isi | WOS:000436958500007 | - |
dc.publisher.place | United Kingdom | - |
dc.identifier.issnl | 2041-1723 | - |