Histone Deacetylase Inhibitor Enhances Recovery after AKI
At present, there are no effective therapies to ameliorate injury, accelerate recovery, or prevent postinjury fibrosis after AKI. Here, we sought to identify candidate compounds that accelerate recovery after AKI by screening for small molecules that increase proliferation of renal progenitor cells...
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| Veröffentlicht in: | Journal of the American Society of Nephrology 2013-06, Vol.24 (6), p.943-953 |
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| creator | CIANCIOLO COSENTINO, Chiara SKRYPNYK, Nataliya I DAVIDSON, Alan J HARRIS, Raymond C DE CAESTECKER, Mark P HUKRIEDE, Neil A BRILLI, Lauren L CHIBA, Takuto NOVITSKAYA, Tatiana WOODS, Clara WEST, James KOROTCHENKO, Vasiliy N MCDERMOTT, Lee DAY, Billy W |
| description | At present, there are no effective therapies to ameliorate injury, accelerate recovery, or prevent postinjury fibrosis after AKI. Here, we sought to identify candidate compounds that accelerate recovery after AKI by screening for small molecules that increase proliferation of renal progenitor cells in zebrafish embryos. One compound identified from this screen was the histone deacetylase inhibitor methyl-4-(phenylthio)butanoate, which we subsequently administered to zebrafish larvae and mice 24-48 hours after inducing AKI. In zebrafish, treatment with the compound increased larval survival and proliferation of renal tubular epithelial cells. In mice, treatment accelerated recovery, reduced postinjury tubular atrophy and interstitial fibrosis, and increased the regenerative capacity of actively cycling renal tubular cells by decreasing the number of cells in G2/M arrest. These data suggest that accelerating recovery may be a viable approach to treating AKI and provide proof of concept that a screen in zebrafish embryos can identify therapeutic candidates for kidney injury. |
| doi_str_mv | 10.1681/asn.2012111055 |
| format | Article |
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Here, we sought to identify candidate compounds that accelerate recovery after AKI by screening for small molecules that increase proliferation of renal progenitor cells in zebrafish embryos. One compound identified from this screen was the histone deacetylase inhibitor methyl-4-(phenylthio)butanoate, which we subsequently administered to zebrafish larvae and mice 24-48 hours after inducing AKI. In zebrafish, treatment with the compound increased larval survival and proliferation of renal tubular epithelial cells. In mice, treatment accelerated recovery, reduced postinjury tubular atrophy and interstitial fibrosis, and increased the regenerative capacity of actively cycling renal tubular cells by decreasing the number of cells in G2/M arrest. These data suggest that accelerating recovery may be a viable approach to treating AKI and provide proof of concept that a screen in zebrafish embryos can identify therapeutic candidates for kidney injury.</description><identifier>ISSN: 1046-6673</identifier><identifier>EISSN: 1533-3450</identifier><identifier>DOI: 10.1681/asn.2012111055</identifier><identifier>PMID: 23620402</identifier><identifier>CODEN: JASNEU</identifier><language>eng</language><publisher>Washington, DC: American Society of Nephrology</publisher><subject>Acute Kidney Injury - drug therapy ; Acute Kidney Injury - enzymology ; Acute Kidney Injury - pathology ; Animals ; Basic Research ; Biological and medical sciences ; Disease Models, Animal ; Fibrosis ; Gentamicins - toxicity ; Histone Deacetylase 1 - antagonists & inhibitors ; Histone Deacetylase 1 - metabolism ; Histone Deacetylase Inhibitors - pharmacology ; Ischemia - drug therapy ; Ischemia - enzymology ; Ischemia - pathology ; Kidney - drug effects ; Kidney - enzymology ; Kidney - pathology ; Male ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Nephrology. Urinary tract diseases ; Phenylbutyrates - pharmacology ; Protein Synthesis Inhibitors - toxicity ; Recovery of Function - drug effects ; Zebrafish ; Zebrafish Proteins - antagonists & inhibitors ; Zebrafish Proteins - metabolism</subject><ispartof>Journal of the American Society of Nephrology, 2013-06, Vol.24 (6), p.943-953</ispartof><rights>2014 INIST-CNRS</rights><rights>Copyright © 2013 by the American Society of Nephrology 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c531t-9cc70286bcbf16d4cd1efaf875db50cf1a792e287c10a98767557528fed9a65b3</citedby><cites>FETCH-LOGICAL-c531t-9cc70286bcbf16d4cd1efaf875db50cf1a792e287c10a98767557528fed9a65b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3665399/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3665399/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27394528$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23620402$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CIANCIOLO COSENTINO, Chiara</creatorcontrib><creatorcontrib>SKRYPNYK, Nataliya I</creatorcontrib><creatorcontrib>DAVIDSON, Alan J</creatorcontrib><creatorcontrib>HARRIS, Raymond C</creatorcontrib><creatorcontrib>DE CAESTECKER, Mark P</creatorcontrib><creatorcontrib>HUKRIEDE, Neil A</creatorcontrib><creatorcontrib>BRILLI, Lauren L</creatorcontrib><creatorcontrib>CHIBA, Takuto</creatorcontrib><creatorcontrib>NOVITSKAYA, Tatiana</creatorcontrib><creatorcontrib>WOODS, Clara</creatorcontrib><creatorcontrib>WEST, James</creatorcontrib><creatorcontrib>KOROTCHENKO, Vasiliy N</creatorcontrib><creatorcontrib>MCDERMOTT, Lee</creatorcontrib><creatorcontrib>DAY, Billy W</creatorcontrib><title>Histone Deacetylase Inhibitor Enhances Recovery after AKI</title><title>Journal of the American Society of Nephrology</title><addtitle>J Am Soc Nephrol</addtitle><description>At present, there are no effective therapies to ameliorate injury, accelerate recovery, or prevent postinjury fibrosis after AKI. Here, we sought to identify candidate compounds that accelerate recovery after AKI by screening for small molecules that increase proliferation of renal progenitor cells in zebrafish embryos. One compound identified from this screen was the histone deacetylase inhibitor methyl-4-(phenylthio)butanoate, which we subsequently administered to zebrafish larvae and mice 24-48 hours after inducing AKI. In zebrafish, treatment with the compound increased larval survival and proliferation of renal tubular epithelial cells. In mice, treatment accelerated recovery, reduced postinjury tubular atrophy and interstitial fibrosis, and increased the regenerative capacity of actively cycling renal tubular cells by decreasing the number of cells in G2/M arrest. These data suggest that accelerating recovery may be a viable approach to treating AKI and provide proof of concept that a screen in zebrafish embryos can identify therapeutic candidates for kidney injury.</description><subject>Acute Kidney Injury - drug therapy</subject><subject>Acute Kidney Injury - enzymology</subject><subject>Acute Kidney Injury - pathology</subject><subject>Animals</subject><subject>Basic Research</subject><subject>Biological and medical sciences</subject><subject>Disease Models, Animal</subject><subject>Fibrosis</subject><subject>Gentamicins - toxicity</subject><subject>Histone Deacetylase 1 - antagonists & inhibitors</subject><subject>Histone Deacetylase 1 - metabolism</subject><subject>Histone Deacetylase Inhibitors - pharmacology</subject><subject>Ischemia - drug therapy</subject><subject>Ischemia - enzymology</subject><subject>Ischemia - pathology</subject><subject>Kidney - drug effects</subject><subject>Kidney - enzymology</subject><subject>Kidney - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Phenylbutyrates - pharmacology</subject><subject>Protein Synthesis Inhibitors - toxicity</subject><subject>Recovery of Function - drug effects</subject><subject>Zebrafish</subject><subject>Zebrafish Proteins - antagonists & inhibitors</subject><subject>Zebrafish Proteins - metabolism</subject><issn>1046-6673</issn><issn>1533-3450</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkE1LAzEQhoMotlavHmUvHrfmY5NsLkKp1RaLgh_nkM1O7Mo2W5K10H_vSmurpxmYZ95hHoQuCR4SkZMbE_2QYkIJIZjzI9QnnLGUZRwfdz3ORCqEZD10FuMnxoRTKU9RjzJBcYZpH6lpFdvGQ3IHxkK7qU2EZOYXVVG1TUgmfmG8hZi8gG3WEDaJcS2EZPQ4O0cnztQRLnZ1gN7vJ2_jaTp_fpiNR_PUckbaVFkrMc1FYQtHRJnZkoAzLpe8LDi2jhipKNBcWoKNyqWQnEtOcwelMoIXbIBut7mrr2IJpQXfBlPrVaiWJmx0Yyr9f-Krhf5o1poJwZlSXcBwG2BDE2MAt98lWP9I1KPXJ32Q2C1c_b24x3-tdcD1DjDRmtqFzlEVD5xkKuteYN-kWXqw</recordid><startdate>20130601</startdate><enddate>20130601</enddate><creator>CIANCIOLO COSENTINO, Chiara</creator><creator>SKRYPNYK, Nataliya I</creator><creator>DAVIDSON, Alan J</creator><creator>HARRIS, Raymond C</creator><creator>DE CAESTECKER, Mark P</creator><creator>HUKRIEDE, Neil A</creator><creator>BRILLI, Lauren L</creator><creator>CHIBA, Takuto</creator><creator>NOVITSKAYA, Tatiana</creator><creator>WOODS, Clara</creator><creator>WEST, James</creator><creator>KOROTCHENKO, Vasiliy N</creator><creator>MCDERMOTT, Lee</creator><creator>DAY, Billy W</creator><general>American Society of Nephrology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20130601</creationdate><title>Histone Deacetylase Inhibitor Enhances Recovery after AKI</title><author>CIANCIOLO COSENTINO, Chiara ; SKRYPNYK, Nataliya I ; DAVIDSON, Alan J ; HARRIS, Raymond C ; DE CAESTECKER, Mark P ; HUKRIEDE, Neil A ; BRILLI, Lauren L ; CHIBA, Takuto ; NOVITSKAYA, Tatiana ; WOODS, Clara ; WEST, James ; KOROTCHENKO, Vasiliy N ; MCDERMOTT, Lee ; DAY, Billy W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c531t-9cc70286bcbf16d4cd1efaf875db50cf1a792e287c10a98767557528fed9a65b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acute Kidney Injury - drug therapy</topic><topic>Acute Kidney Injury - enzymology</topic><topic>Acute Kidney Injury - pathology</topic><topic>Animals</topic><topic>Basic Research</topic><topic>Biological and medical sciences</topic><topic>Disease Models, Animal</topic><topic>Fibrosis</topic><topic>Gentamicins - toxicity</topic><topic>Histone Deacetylase 1 - antagonists & inhibitors</topic><topic>Histone Deacetylase 1 - metabolism</topic><topic>Histone Deacetylase Inhibitors - pharmacology</topic><topic>Ischemia - drug therapy</topic><topic>Ischemia - enzymology</topic><topic>Ischemia - pathology</topic><topic>Kidney - drug effects</topic><topic>Kidney - enzymology</topic><topic>Kidney - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Phenylbutyrates - pharmacology</topic><topic>Protein Synthesis Inhibitors - toxicity</topic><topic>Recovery of Function - drug effects</topic><topic>Zebrafish</topic><topic>Zebrafish Proteins - antagonists & inhibitors</topic><topic>Zebrafish Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CIANCIOLO COSENTINO, Chiara</creatorcontrib><creatorcontrib>SKRYPNYK, Nataliya I</creatorcontrib><creatorcontrib>DAVIDSON, Alan J</creatorcontrib><creatorcontrib>HARRIS, Raymond C</creatorcontrib><creatorcontrib>DE CAESTECKER, Mark P</creatorcontrib><creatorcontrib>HUKRIEDE, Neil A</creatorcontrib><creatorcontrib>BRILLI, Lauren L</creatorcontrib><creatorcontrib>CHIBA, Takuto</creatorcontrib><creatorcontrib>NOVITSKAYA, Tatiana</creatorcontrib><creatorcontrib>WOODS, Clara</creatorcontrib><creatorcontrib>WEST, James</creatorcontrib><creatorcontrib>KOROTCHENKO, Vasiliy N</creatorcontrib><creatorcontrib>MCDERMOTT, Lee</creatorcontrib><creatorcontrib>DAY, Billy W</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of the American Society of Nephrology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CIANCIOLO COSENTINO, Chiara</au><au>SKRYPNYK, Nataliya I</au><au>DAVIDSON, Alan J</au><au>HARRIS, Raymond C</au><au>DE CAESTECKER, Mark P</au><au>HUKRIEDE, Neil A</au><au>BRILLI, Lauren L</au><au>CHIBA, Takuto</au><au>NOVITSKAYA, Tatiana</au><au>WOODS, Clara</au><au>WEST, James</au><au>KOROTCHENKO, Vasiliy N</au><au>MCDERMOTT, Lee</au><au>DAY, Billy W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Histone Deacetylase Inhibitor Enhances Recovery after AKI</atitle><jtitle>Journal of the American Society of Nephrology</jtitle><addtitle>J Am Soc Nephrol</addtitle><date>2013-06-01</date><risdate>2013</risdate><volume>24</volume><issue>6</issue><spage>943</spage><epage>953</epage><pages>943-953</pages><issn>1046-6673</issn><eissn>1533-3450</eissn><coden>JASNEU</coden><abstract>At present, there are no effective therapies to ameliorate injury, accelerate recovery, or prevent postinjury fibrosis after AKI. Here, we sought to identify candidate compounds that accelerate recovery after AKI by screening for small molecules that increase proliferation of renal progenitor cells in zebrafish embryos. One compound identified from this screen was the histone deacetylase inhibitor methyl-4-(phenylthio)butanoate, which we subsequently administered to zebrafish larvae and mice 24-48 hours after inducing AKI. In zebrafish, treatment with the compound increased larval survival and proliferation of renal tubular epithelial cells. In mice, treatment accelerated recovery, reduced postinjury tubular atrophy and interstitial fibrosis, and increased the regenerative capacity of actively cycling renal tubular cells by decreasing the number of cells in G2/M arrest. These data suggest that accelerating recovery may be a viable approach to treating AKI and provide proof of concept that a screen in zebrafish embryos can identify therapeutic candidates for kidney injury.</abstract><cop>Washington, DC</cop><pub>American Society of Nephrology</pub><pmid>23620402</pmid><doi>10.1681/asn.2012111055</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1046-6673 |
| ispartof | Journal of the American Society of Nephrology, 2013-06, Vol.24 (6), p.943-953 |
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| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Acute Kidney Injury - drug therapy Acute Kidney Injury - enzymology Acute Kidney Injury - pathology Animals Basic Research Biological and medical sciences Disease Models, Animal Fibrosis Gentamicins - toxicity Histone Deacetylase 1 - antagonists & inhibitors Histone Deacetylase 1 - metabolism Histone Deacetylase Inhibitors - pharmacology Ischemia - drug therapy Ischemia - enzymology Ischemia - pathology Kidney - drug effects Kidney - enzymology Kidney - pathology Male Medical sciences Mice Mice, Inbred BALB C Nephrology. Urinary tract diseases Phenylbutyrates - pharmacology Protein Synthesis Inhibitors - toxicity Recovery of Function - drug effects Zebrafish Zebrafish Proteins - antagonists & inhibitors Zebrafish Proteins - metabolism |
| title | Histone Deacetylase Inhibitor Enhances Recovery after AKI |
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