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Article: Overexpression of iNOS and down-regulation of BMPs-2, 4 and 7 in retinoic acid induced cleft palate formation

TitleOverexpression of iNOS and down-regulation of BMPs-2, 4 and 7 in retinoic acid induced cleft palate formation
Authors
Issue Date2004
PublisherHistology and Histopathology. The Journal's web site is located at http://www.hh.um.es
Citation
Histology And Histopathology, 2004, v. 19 n. 1, p. 95-104 How to Cite?
AbstractThe present work studied the induction of cleft palate formation in embryos developed from pregnant BALB/c mice treated orally with retinoic acid (RA). Previous studies on mature somatic cell types showed that RA exerted inhibitory effects on inducible nitric oxide synthase (iNOS) production. For the first time, our study has shown that RA actually stimulates significant expression of iNOS at specific zones of the affected embryonic palatal tissues at three consecutive stages, from gestation day 13 (GD13) to day 16 (GD16). Enzymatically, iNOS facilitates intracellular nitric oxide (NO) synthesis from L-arginine. When NO reacts with reactive superoxides it may result in irreparable cell injury. NO was also reported to induce apoptosis in some mammalian cell systems. Based on our findings, we propose that such an increase in NO production might be associated with apoptosis in the embryonic palatal tissues in the RA-treated mice. The detrimental effects of NO resulted in a reduction in proliferating palatal cells and therefore disturbed the normal plasticity of the palatal shelves. With iNOS overexpression, our findings also showed that there was significant concomitant down-regulation in the expressions of Bone Morphogenetic Proteins (BMPs) -2, 4, and 7 with regional variations particularly in the palatal mesenchymal cells for those embryos developing cleft palate. Since specific spatial and temporal expressions of BMPs -2, 4, and 7 are critical during normal palatal morphogenesis, any deficiency in the epithelialmesenchymal interaction may result in retarding growth at the embryonic palatal shelves. Taken together, our study has demonstrated cleft palate formation in the BALB/c embryos involved overexpression of iNOS and down-regulation of BMPs- 2, 4 and 7.
Persistent Identifierhttp://hdl.handle.net/10722/67616
ISSN
2015 Impact Factor: 1.875
2015 SCImago Journal Rankings: 0.805
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorHo, CTen_HK
dc.contributor.authorLau, TYHen_HK
dc.contributor.authorJin, Yen_HK
dc.contributor.authorLu, HBen_HK
dc.contributor.authorLiong, Een_HK
dc.contributor.authorLeung, KMen_HK
dc.contributor.authorTipoe, GLen_HK
dc.date.accessioned2010-09-06T05:56:43Z-
dc.date.available2010-09-06T05:56:43Z-
dc.date.issued2004en_HK
dc.identifier.citationHistology And Histopathology, 2004, v. 19 n. 1, p. 95-104en_HK
dc.identifier.issn0213-3911en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67616-
dc.description.abstractThe present work studied the induction of cleft palate formation in embryos developed from pregnant BALB/c mice treated orally with retinoic acid (RA). Previous studies on mature somatic cell types showed that RA exerted inhibitory effects on inducible nitric oxide synthase (iNOS) production. For the first time, our study has shown that RA actually stimulates significant expression of iNOS at specific zones of the affected embryonic palatal tissues at three consecutive stages, from gestation day 13 (GD13) to day 16 (GD16). Enzymatically, iNOS facilitates intracellular nitric oxide (NO) synthesis from L-arginine. When NO reacts with reactive superoxides it may result in irreparable cell injury. NO was also reported to induce apoptosis in some mammalian cell systems. Based on our findings, we propose that such an increase in NO production might be associated with apoptosis in the embryonic palatal tissues in the RA-treated mice. The detrimental effects of NO resulted in a reduction in proliferating palatal cells and therefore disturbed the normal plasticity of the palatal shelves. With iNOS overexpression, our findings also showed that there was significant concomitant down-regulation in the expressions of Bone Morphogenetic Proteins (BMPs) -2, 4, and 7 with regional variations particularly in the palatal mesenchymal cells for those embryos developing cleft palate. Since specific spatial and temporal expressions of BMPs -2, 4, and 7 are critical during normal palatal morphogenesis, any deficiency in the epithelialmesenchymal interaction may result in retarding growth at the embryonic palatal shelves. Taken together, our study has demonstrated cleft palate formation in the BALB/c embryos involved overexpression of iNOS and down-regulation of BMPs- 2, 4 and 7.en_HK
dc.languageengen_HK
dc.publisherHistology and Histopathology. The Journal's web site is located at http://www.hh.um.esen_HK
dc.relation.ispartofHistology and Histopathologyen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshBone Morphogenetic Protein 4en_HK
dc.subject.meshBone Morphogenetic Proteins - genetics - metabolismen_HK
dc.subject.meshCleft Palate - chemically induced - embryology - metabolismen_HK
dc.subject.meshDown-Regulationen_HK
dc.subject.meshGene Expression Regulation, Developmental - drug effectsen_HK
dc.subject.meshImmunohistochemistryen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Inbred BALB Cen_HK
dc.subject.meshNitric Oxide Synthase - drug effects - metabolismen_HK
dc.subject.meshNitric Oxide Synthase Type IIen_HK
dc.subject.meshTeratogens - pharmacologyen_HK
dc.subject.meshTime Factorsen_HK
dc.subject.meshTissue Distribution - drug effectsen_HK
dc.subject.meshTretinoin - pharmacologyen_HK
dc.titleOverexpression of iNOS and down-regulation of BMPs-2, 4 and 7 in retinoic acid induced cleft palate formationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0213-3911&volume=19&spage=95&epage=104&date=2004&atitle=Overexpression+of+iNOS+and+down-regulation+of+BMPs-2,+4+and+7+in+retinoic+acid+induced+cleft+palate+formationen_HK
dc.identifier.emailTipoe, GL:tgeorge@hkucc.hku.hken_HK
dc.identifier.authorityTipoe, GL=rp00371en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.pmid14702176-
dc.identifier.scopuseid_2-s2.0-1642515051en_HK
dc.identifier.hkuros86040en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-1642515051&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume19en_HK
dc.identifier.issue1en_HK
dc.identifier.spage95en_HK
dc.identifier.epage104en_HK
dc.identifier.isiWOS:000188355400013-
dc.publisher.placeSpainen_HK
dc.identifier.scopusauthoridHo, CT=55222467600en_HK
dc.identifier.scopusauthoridLau, TYH=26323763000en_HK
dc.identifier.scopusauthoridJin, Y=26643271200en_HK
dc.identifier.scopusauthoridLu, HB=7404843896en_HK
dc.identifier.scopusauthoridLiong, E=6602732210en_HK
dc.identifier.scopusauthoridLeung, KM=7401860685en_HK
dc.identifier.scopusauthoridTipoe, GL=7003550610en_HK

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