All-trans retinoic acid modulates mitogen-activated protein kinase pathway activation in human scleral fibroblasts through retinoic acid receptor beta
Identifieur interne : 000534 ( Main/Exploration ); précédent : 000533; suivant : 000535All-trans retinoic acid modulates mitogen-activated protein kinase pathway activation in human scleral fibroblasts through retinoic acid receptor beta
Auteurs : Lijun Huo [République populaire de Chine] ; Dongmei Cui [République populaire de Chine] ; Xiao Yang [République populaire de Chine] ; Zhenya Gao [République populaire de Chine] ; Klaus Trier [Danemark] ; Junwen Zeng [République populaire de Chine]Source :
- Molecular Vision [ 1090-0535 ] ; 2013.
Abstract
All-trans retinoic acid (ATRA) is known to inhibit the proliferation of human scleral fibroblasts (HSFs) and to modulate the scleral intercellular matrix composition, and may therefore serve as a mediator for controlling eye growth. Cell proliferation is regulated by the mitogen-activated protein kinase (MAPK) pathway. The aim of the current study was to investigate whether changed activation of the MAPK pathway could be involved in the response of HSFs exposed to ATRA.
HSFs were cultured in Dulbecco Modified Eagle's Medium/F12 (DMEM/F12) and exposed to 1 μmol/l ATRA for 10 min, 30 min, 1 h, 8 h, or 24 h. The activation of extracellular signal-regulated kinase (ERK 1/2), p38, and c-Jun N-terminal kinase (JNK) in HSFs was assessed with western blot analysis and immunocytofluorescence.
After exposure to ATRA for 24 h, the HSFs appeared shrunken and thinner than the control cells. The intercellular spaces were wider, and the HSFs appeared less numerous than in the control culture. Western blot showed decreased activation of ERK 1/2 in the HSFs from 30 min (p=0.01) to 24 h (p<0.01) after the start of exposure to ATRA, and increased activation of the JNK protein from 10 to 30 min (p<0.01) after the start of exposure to ATRA. Indirect immunofluorescence confirmed changes in activation of ERK 1/2 and JNK in HSFs exposed to ATRA. No change in activation of p38 in HSFs was observed after exposure to ATRA. Pretreatment of the HSFs with LE135, an antagonist of retinoic acid receptor beta (RARβ), abolished the ATRA-induced changes inactivation of ERK 1/2 and JNK.
ATRA inhibits HSF proliferation by a mechanism associated with modulation of ERK 1/2 and JNK activation and depends on stimulation of retinoic acid receptor beta.
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PubMed: 23946634
PubMed Central: 3742120
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China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Gao, Zhenya" sort="Gao, Zhenya" uniqKey="Gao Z" first="Zhenya" last="Gao">Zhenya Gao</name><affiliation wicri:level="3"><nlm:aff id="aff1">State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P. R. 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China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23946634</idno><idno type="pmc">3742120</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742120</idno><idno type="RBID">PMC:3742120</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000153</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000153</idno><idno type="wicri:Area/Pmc/Curation">000153</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000153</idno><idno type="wicri:Area/Pmc/Checkpoint">000094</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000094</idno><idno type="wicri:Area/Ncbi/Merge">000617</idno><idno type="wicri:Area/Ncbi/Curation">000617</idno><idno type="wicri:Area/Ncbi/Checkpoint">000617</idno><idno type="wicri:Area/Main/Merge">000536</idno><idno type="wicri:Area/Main/Curation">000534</idno><idno type="wicri:Area/Main/Exploration">000534</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">All-trans retinoic acid modulates mitogen-activated protein kinase pathway activation in human scleral fibroblasts through retinoic acid receptor beta</title><author><name sortKey="Huo, Lijun" sort="Huo, Lijun" uniqKey="Huo L" first="Lijun" last="Huo">Lijun Huo</name><affiliation wicri:level="3"><nlm:aff id="aff1">State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2">The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The First Affiliated Hospital, Sun Yat-sen University, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Cui, Dongmei" sort="Cui, Dongmei" uniqKey="Cui D" first="Dongmei" last="Cui">Dongmei Cui</name><affiliation wicri:level="3"><nlm:aff id="aff1">State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Yang, Xiao" sort="Yang, Xiao" uniqKey="Yang X" first="Xiao" last="Yang">Xiao Yang</name><affiliation wicri:level="3"><nlm:aff id="aff1">State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Gao, Zhenya" sort="Gao, Zhenya" uniqKey="Gao Z" first="Zhenya" last="Gao">Zhenya Gao</name><affiliation wicri:level="3"><nlm:aff id="aff1">State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Trier, Klaus" sort="Trier, Klaus" uniqKey="Trier K" first="Klaus" last="Trier">Klaus Trier</name><affiliation wicri:level="1"><nlm:aff id="aff3">Trier Research Laboratories, Hellerup, Denmark</nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Trier Research Laboratories, Hellerup</wicri:regionArea><wicri:noRegion>Hellerup</wicri:noRegion></affiliation></author><author><name sortKey="Zeng, Junwen" sort="Zeng, Junwen" uniqKey="Zeng J" first="Junwen" last="Zeng">Junwen Zeng</name><affiliation wicri:level="3"><nlm:aff id="aff1">State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author></analytic><series><title level="j">Molecular Vision</title><idno type="eISSN">1090-0535</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Purpose</title><p>All-trans retinoic acid (ATRA) is known to inhibit the proliferation of human scleral fibroblasts (HSFs) and to modulate the scleral intercellular matrix composition, and may therefore serve as a mediator for controlling eye growth. Cell proliferation is regulated by the mitogen-activated protein kinase (MAPK) pathway. The aim of the current study was to investigate whether changed activation of the MAPK pathway could be involved in the response of HSFs exposed to ATRA.</p></sec><sec><title>Methods</title><p>HSFs were cultured in Dulbecco Modified Eagle's Medium/F12 (DMEM/F12) and exposed to 1 μmol/l ATRA for 10 min, 30 min, 1 h, 8 h, or 24 h. The activation of extracellular signal-regulated kinase (ERK 1/2), p38, and c-Jun N-terminal kinase (JNK) in HSFs was assessed with western blot analysis and immunocytofluorescence.</p></sec><sec><title>Results</title><p>After exposure to ATRA for 24 h, the HSFs appeared shrunken and thinner than the control cells. The intercellular spaces were wider, and the HSFs appeared less numerous than in the control culture. Western blot showed decreased activation of ERK 1/2 in the HSFs from 30 min (p=0.01) to 24 h (p<0.01) after the start of exposure to ATRA, and increased activation of the JNK protein from 10 to 30 min (p<0.01) after the start of exposure to ATRA. Indirect immunofluorescence confirmed changes in activation of ERK 1/2 and JNK in HSFs exposed to ATRA. No change in activation of p38 in HSFs was observed after exposure to ATRA. Pretreatment of the HSFs with LE135, an antagonist of retinoic acid receptor beta (RARβ), abolished the ATRA-induced changes inactivation of ERK 1/2 and JNK.</p></sec><sec><title>Conclusions</title><p>ATRA inhibits HSF proliferation by a mechanism associated with modulation of ERK 1/2 and JNK activation and depends on stimulation of retinoic acid receptor beta.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="He, M" uniqKey="He M">M He</name></author><author><name sortKey="Zeng, J" uniqKey="Zeng J">J Zeng</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name></author><author><name sortKey="Xu, J" uniqKey="Xu J">J Xu</name></author><author><name sortKey="Pokharel, Gp" uniqKey="Pokharel G">GP Pokharel</name></author><author><name sortKey="Ellwein, Lb" uniqKey="Ellwein L">LB Ellwein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chang, L" uniqKey="Chang L">L Chang</name></author><author><name sortKey="Pan, Cw" uniqKey="Pan C">CW Pan</name></author><author><name sortKey="Ohno Matsui, K" uniqKey="Ohno Matsui K">K Ohno-Matsui</name></author><author><name sortKey="Lin, X" uniqKey="Lin X">X Lin</name></author><author><name sortKey="Lin, X" uniqKey="Lin X">X Lin</name></author><author><name sortKey="Cheung, Gc" uniqKey="Cheung G">GC Cheung</name></author><author><name sortKey="Gazzard, G" uniqKey="Gazzard G">G Gazzard</name></author><author><name sortKey="Koh, V" uniqKey="Koh V">V Koh</name></author><author><name sortKey="Hamzah, H" uniqKey="Hamzah H">H Hamzah</name></author><author><name sortKey="Tai, Es" uniqKey="Tai E">ES Tai</name></author><author><name sortKey="Lim, Sc" uniqKey="Lim S">SC Lim</name></author><author><name sortKey="Mitchell, P" uniqKey="Mitchell P">P Mitchell</name></author><author><name sortKey="Young, Tl" uniqKey="Young T">TL Young</name></author><author><name sortKey="Aung, T" uniqKey="Aung T">T Aung</name></author><author><name sortKey="Wong, Ty" uniqKey="Wong T">TY Wong</name></author><author><name sortKey="Saw, Sm" uniqKey="Saw S">SM Saw</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kusakari, T" uniqKey="Kusakari T">T Kusakari</name></author><author><name sortKey="Sato, T" uniqKey="Sato T">T Sato</name></author><author><name sortKey="Tokoro, T" uniqKey="Tokoro T">T Tokoro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcbrien, Na" uniqKey="Mcbrien N">NA McBrien</name></author><author><name sortKey="Cornell, Lm" uniqKey="Cornell L">LM Cornell</name></author><author><name sortKey="Gentle, A" uniqKey="Gentle A">A Gentle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcbrien, Na" uniqKey="Mcbrien N">NA McBrien</name></author><author><name sortKey="Lawlor, P" uniqKey="Lawlor P">P Lawlor</name></author><author><name sortKey="Gentle, A" uniqKey="Gentle A">A Gentle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Means, Al" uniqKey="Means A">AL Means</name></author><author><name sortKey="Gudas, Lj" uniqKey="Gudas L">LJ Gudas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcfadden, Sa" uniqKey="Mcfadden S">SA McFadden</name></author><author><name sortKey="Howlett, Mh" uniqKey="Howlett M">MH Howlett</name></author><author><name sortKey="Mertz, Jr" uniqKey="Mertz J">JR Mertz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mertz, Jr" uniqKey="Mertz J">JR Mertz</name></author><author><name sortKey="Wallman, J" uniqKey="Wallman J">J Wallman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yan, Ds" uniqKey="Yan D">DS Yan</name></author><author><name sortKey="Zhou, Xt" uniqKey="Zhou X">XT Zhou</name></author><author><name sortKey="Chen, Xy" uniqKey="Chen X">XY Chen</name></author><author><name sortKey="Lu, F" uniqKey="Lu F">F Lu</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J Wang</name></author><author><name sortKey="Hu, Dn" uniqKey="Hu D">DN Hu</name></author><author><name sortKey="Qu, J" uniqKey="Qu J">J. 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D">D Bogojević</name></author><author><name sortKey="Petrovi, A" uniqKey="Petrovi A">A Petrović</name></author><author><name sortKey="Jovanovi, S" uniqKey="Jovanovi S">S Jovanović</name></author><author><name sortKey="Ilic, M" uniqKey="Ilic M">M Ilic</name></author><author><name sortKey="Ivanovi Matic, S" uniqKey="Ivanovi Matic S">S Ivanović Matic</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kafienah, W" uniqKey="Kafienah W">W Kafienah</name></author><author><name sortKey="Mistry, S" uniqKey="Mistry S">S Mistry</name></author><author><name sortKey="Perry, Mj" uniqKey="Perry M">MJ Perry</name></author><author><name sortKey="Politopoulou, G" uniqKey="Politopoulou G">G Politopoulou</name></author><author><name sortKey="Hollander, Ap" uniqKey="Hollander A">AP Hollander</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, J" uniqKey="Huang J">J Huang</name></author><author><name sortKey="Qu, Xm" uniqKey="Qu X">XM Qu</name></author><author><name sortKey="Chu, Ry" uniqKey="Chu R">RY Chu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Troilo, D" uniqKey="Troilo D">D Troilo</name></author><author><name sortKey="Nickla, Dl" uniqKey="Nickla D">DL Nickla</name></author><author><name sortKey="Mertz, Jr" uniqKey="Mertz J">JR Mertz</name></author><author><name sortKey="Summers, Rj" uniqKey="Summers R">RJ Summers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nishimoto, S" uniqKey="Nishimoto S">S Nishimoto</name></author><author><name sortKey="Nishida, E" uniqKey="Nishida E">E Nishida</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Danemark</li><li>République populaire de Chine</li></country><region><li>Guangdong</li></region><settlement><li>Jiangmen</li></settlement></list><tree><country name="République populaire de Chine"><region name="Guangdong"><name sortKey="Huo, Lijun" sort="Huo, Lijun" uniqKey="Huo L" first="Lijun" last="Huo">Lijun Huo</name></region><name sortKey="Cui, Dongmei" sort="Cui, Dongmei" uniqKey="Cui D" first="Dongmei" last="Cui">Dongmei Cui</name><name sortKey="Gao, Zhenya" sort="Gao, Zhenya" uniqKey="Gao Z" first="Zhenya" last="Gao">Zhenya Gao</name><name sortKey="Huo, Lijun" sort="Huo, Lijun" uniqKey="Huo L" first="Lijun" last="Huo">Lijun Huo</name><name sortKey="Yang, Xiao" sort="Yang, Xiao" uniqKey="Yang X" first="Xiao" last="Yang">Xiao Yang</name><name sortKey="Zeng, Junwen" sort="Zeng, Junwen" uniqKey="Zeng J" first="Junwen" last="Zeng">Junwen Zeng</name></country><country name="Danemark"><noRegion><name sortKey="Trier, Klaus" sort="Trier, Klaus" uniqKey="Trier K" first="Klaus" last="Trier">Klaus Trier</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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