The senotherapeutic drug ABT-737 disrupts aberrant p21 expression to restore liver regeneration in adult mice
Young mammals possess a limited regenerative capacity in some tissues, which is lost upon maturation. We investigated whether cellular senescence might play a role in such loss during liver regeneration. We found that following partial hepatectomy, the senescence-associated genes p21, p16 , and p19...
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| Veröffentlicht in: | Genes & development 2020-04, Vol.34 (7-8), p.489-494 |
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| creator | Ritschka, Birgit Knauer-Meyer, Tania Gonçalves, Daniel Sampaio Mas, Alba Plassat, Jean-Luc Durik, Matej Jacobs, Hugues Pedone, Elisa Di Vicino, Umberto Cosma, Maria Pia Keyes, William M |
| description | Young mammals possess a limited regenerative capacity in some tissues, which is lost upon maturation. We investigated whether cellular senescence might play a role in such loss during liver regeneration. We found that following partial hepatectomy, the senescence-associated genes p21, p16
, and p19
become dynamically expressed in different cell types when regenerative capacity decreases, but without a full senescent response. However, we show that treatment with a senescence-inhibiting drug improves regeneration, by disrupting aberrantly prolonged p21 expression. This work suggests that senescence may initially develop from heterogeneous cellular responses, and that senotherapeutic drugs might be useful in promoting organ regeneration. |
| doi_str_mv | 10.1101/gad.332643.119 |
| format | Article |
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, and p19
become dynamically expressed in different cell types when regenerative capacity decreases, but without a full senescent response. However, we show that treatment with a senescence-inhibiting drug improves regeneration, by disrupting aberrantly prolonged p21 expression. This work suggests that senescence may initially develop from heterogeneous cellular responses, and that senotherapeutic drugs might be useful in promoting organ regeneration.</description><identifier>ISSN: 0890-9369</identifier><identifier>EISSN: 1549-5477</identifier><identifier>DOI: 10.1101/gad.332643.119</identifier><identifier>PMID: 32139422</identifier><language>eng</language><publisher>United States: Cold Spring Harbor Laboratory Press</publisher><subject>Cellular Biology ; Life Sciences ; Research Communication</subject><ispartof>Genes & development, 2020-04, Vol.34 (7-8), p.489-494</ispartof><rights>2020 Ritschka et al.; Published by Cold Spring Harbor Laboratory Press.</rights><rights>Attribution</rights><rights>2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c490t-1db1e584e8b4b87448f40b3ee3c05d9c945a1f5fcbcebeec9b5a0e5e61f60dad3</citedby><cites>FETCH-LOGICAL-c490t-1db1e584e8b4b87448f40b3ee3c05d9c945a1f5fcbcebeec9b5a0e5e61f60dad3</cites><orcidid>0000-0002-8917-2268</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111259/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111259/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32139422$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03715508$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Ritschka, Birgit</creatorcontrib><creatorcontrib>Knauer-Meyer, Tania</creatorcontrib><creatorcontrib>Gonçalves, Daniel Sampaio</creatorcontrib><creatorcontrib>Mas, Alba</creatorcontrib><creatorcontrib>Plassat, Jean-Luc</creatorcontrib><creatorcontrib>Durik, Matej</creatorcontrib><creatorcontrib>Jacobs, Hugues</creatorcontrib><creatorcontrib>Pedone, Elisa</creatorcontrib><creatorcontrib>Di Vicino, Umberto</creatorcontrib><creatorcontrib>Cosma, Maria Pia</creatorcontrib><creatorcontrib>Keyes, William M</creatorcontrib><title>The senotherapeutic drug ABT-737 disrupts aberrant p21 expression to restore liver regeneration in adult mice</title><title>Genes & development</title><addtitle>Genes Dev</addtitle><description>Young mammals possess a limited regenerative capacity in some tissues, which is lost upon maturation. We investigated whether cellular senescence might play a role in such loss during liver regeneration. We found that following partial hepatectomy, the senescence-associated genes p21, p16
, and p19
become dynamically expressed in different cell types when regenerative capacity decreases, but without a full senescent response. However, we show that treatment with a senescence-inhibiting drug improves regeneration, by disrupting aberrantly prolonged p21 expression. This work suggests that senescence may initially develop from heterogeneous cellular responses, and that senotherapeutic drugs might be useful in promoting organ regeneration.</description><subject>Cellular Biology</subject><subject>Life Sciences</subject><subject>Research Communication</subject><issn>0890-9369</issn><issn>1549-5477</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNpdkc9vFCEUx4nR2G316tFw1MOsMMDMcDHZNmqbbNLL9kz48WYXMzOMwGzqfy-brY32BF_elw_v8UXoAyVrSgn9stduzVjdcFa0fIVWVHBZCd62r9GKdJJUkjXyAl2m9JMQ0pCmeYsuWE2Z5HW9QuPuADjBFPIBop5hyd5iF5c93lzvqpa12PkUlzknrA3EqKeM55pieJwjpOTDhHPAZZtDBDz4I8Si9jAVWj5V_YS1W4aMR2_hHXrT6yHB-6f1Cj18_7a7ua229z_ubjbbynJJckWdoSA6Dp3hpms573pODANglggnreRC01701lgwAFYaoQkIaGjfEKcdu0Jfz9x5MSM4C1OOelBz9KOOv1XQXv1fmfxB7cNRtZTSWsgC-HwGHF5cu91s1emMsJYKQbojLd5PT4_F8GspP6FGnywMg54gLEnVrOWsoVKQYl2frTaGlCL0z2xK1ClPVfJU5zyLPvXx8d9Bnu1_A2R_AH5cnhI</recordid><startdate>20200401</startdate><enddate>20200401</enddate><creator>Ritschka, Birgit</creator><creator>Knauer-Meyer, Tania</creator><creator>Gonçalves, Daniel Sampaio</creator><creator>Mas, Alba</creator><creator>Plassat, Jean-Luc</creator><creator>Durik, Matej</creator><creator>Jacobs, Hugues</creator><creator>Pedone, Elisa</creator><creator>Di Vicino, Umberto</creator><creator>Cosma, Maria Pia</creator><creator>Keyes, William M</creator><general>Cold Spring Harbor Laboratory Press</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8917-2268</orcidid></search><sort><creationdate>20200401</creationdate><title>The senotherapeutic drug ABT-737 disrupts aberrant p21 expression to restore liver regeneration in adult mice</title><author>Ritschka, Birgit ; Knauer-Meyer, Tania ; Gonçalves, Daniel Sampaio ; Mas, Alba ; Plassat, Jean-Luc ; Durik, Matej ; Jacobs, Hugues ; Pedone, Elisa ; Di Vicino, Umberto ; Cosma, Maria Pia ; Keyes, William M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c490t-1db1e584e8b4b87448f40b3ee3c05d9c945a1f5fcbcebeec9b5a0e5e61f60dad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Cellular Biology</topic><topic>Life Sciences</topic><topic>Research Communication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ritschka, Birgit</creatorcontrib><creatorcontrib>Knauer-Meyer, Tania</creatorcontrib><creatorcontrib>Gonçalves, Daniel Sampaio</creatorcontrib><creatorcontrib>Mas, Alba</creatorcontrib><creatorcontrib>Plassat, Jean-Luc</creatorcontrib><creatorcontrib>Durik, Matej</creatorcontrib><creatorcontrib>Jacobs, Hugues</creatorcontrib><creatorcontrib>Pedone, Elisa</creatorcontrib><creatorcontrib>Di Vicino, Umberto</creatorcontrib><creatorcontrib>Cosma, Maria Pia</creatorcontrib><creatorcontrib>Keyes, William M</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genes & development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ritschka, Birgit</au><au>Knauer-Meyer, Tania</au><au>Gonçalves, Daniel Sampaio</au><au>Mas, Alba</au><au>Plassat, Jean-Luc</au><au>Durik, Matej</au><au>Jacobs, Hugues</au><au>Pedone, Elisa</au><au>Di Vicino, Umberto</au><au>Cosma, Maria Pia</au><au>Keyes, William M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The senotherapeutic drug ABT-737 disrupts aberrant p21 expression to restore liver regeneration in adult mice</atitle><jtitle>Genes & development</jtitle><addtitle>Genes Dev</addtitle><date>2020-04-01</date><risdate>2020</risdate><volume>34</volume><issue>7-8</issue><spage>489</spage><epage>494</epage><pages>489-494</pages><issn>0890-9369</issn><eissn>1549-5477</eissn><abstract>Young mammals possess a limited regenerative capacity in some tissues, which is lost upon maturation. We investigated whether cellular senescence might play a role in such loss during liver regeneration. We found that following partial hepatectomy, the senescence-associated genes p21, p16
, and p19
become dynamically expressed in different cell types when regenerative capacity decreases, but without a full senescent response. However, we show that treatment with a senescence-inhibiting drug improves regeneration, by disrupting aberrantly prolonged p21 expression. This work suggests that senescence may initially develop from heterogeneous cellular responses, and that senotherapeutic drugs might be useful in promoting organ regeneration.</abstract><cop>United States</cop><pub>Cold Spring Harbor Laboratory Press</pub><pmid>32139422</pmid><doi>10.1101/gad.332643.119</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-8917-2268</orcidid><oa>free_for_read</oa></addata></record> |
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| title | The senotherapeutic drug ABT-737 disrupts aberrant p21 expression to restore liver regeneration in adult mice |
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