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dc.contributor.authorMa, Ming
dc.contributor.authorTian, Xin
dc.contributor.authorIgarashi, Peter
dc.contributor.authorPazour, Gregory J.
dc.contributor.authorSomlo, Stefan
dc.date2022-08-11T08:08:31.000
dc.date.accessioned2022-08-23T15:57:56Z
dc.date.available2022-08-23T15:57:56Z
dc.date.issued2013-09-01
dc.date.submitted2015-03-24
dc.identifier.citationNat Genet. 2013 Sep;45(9):1004-12. doi: 10.1038/ng.2715. Epub 2013 Jul 28. <a href="http://dx.doi.org/10.1038/ng.2715">Link to article on publisher's site</a>
dc.identifier.issn1061-4036 (Linking)
dc.identifier.doi10.1038/ng.2715
dc.identifier.pmid23892607
dc.identifier.urihttp://hdl.handle.net/20.500.14038/30318
dc.description.abstractKidney cysts occur following inactivation of polycystins in otherwise intact cilia or following complete removal of cilia by inactivation of intraflagellar transport-related proteins. We investigated the mechanisms of cyst formation in these two distinct processes by combining conditional inactivation of polycystins with concomitant ablation of cilia in developing and adult kidney and liver. We found that loss of intact cilia suppressed cyst growth following inactivation of polycystins and that the severity of cystic disease was directly related to the length of time between the initial loss of the polycystin proteins and the subsequent involution of cilia. This cilia-dependent cyst growth was not explained by activation of the MAPK/ERK, mTOR or cAMP pathways and is likely to be distinct from the mechanism of cyst growth following complete loss of cilia. These data establish the existence of a new pathway defined by polycystin-dependent inhibition and cilia-dependent activation that promotes rapid cyst growth.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23892607&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3758452/
dc.subjectAnimals
dc.subjectCilia
dc.subjectCysts
dc.subjectDisease Models, Animal
dc.subjectGenotype
dc.subjectMice
dc.subjectMice, Knockout
dc.subjectMutation
dc.subjectPhenotype
dc.subjectPolycystic Kidney, Autosomal Dominant
dc.subjectTRPP Cation Channels
dc.subjectMolecular Genetics
dc.titleLoss of cilia suppresses cyst growth in genetic models of autosomal dominant polycystic kidney disease
dc.typeJournal Article
dc.source.journaltitleNature genetics
dc.source.volume45
dc.source.issue9
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/585
dc.identifier.contextkey6889250
html.description.abstract<p>Kidney cysts occur following inactivation of polycystins in otherwise intact cilia or following complete removal of cilia by inactivation of intraflagellar transport-related proteins. We investigated the mechanisms of cyst formation in these two distinct processes by combining conditional inactivation of polycystins with concomitant ablation of cilia in developing and adult kidney and liver. We found that loss of intact cilia suppressed cyst growth following inactivation of polycystins and that the severity of cystic disease was directly related to the length of time between the initial loss of the polycystin proteins and the subsequent involution of cilia. This cilia-dependent cyst growth was not explained by activation of the MAPK/ERK, mTOR or cAMP pathways and is likely to be distinct from the mechanism of cyst growth following complete loss of cilia. These data establish the existence of a new pathway defined by polycystin-dependent inhibition and cilia-dependent activation that promotes rapid cyst growth.</p>
dc.identifier.submissionpathfaculty_pubs/585
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages1004-12


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