dc.contributor.author | Felekkis, Kyriacos N. | en |
dc.contributor.author | Koupepidou, P. | en |
dc.contributor.author | Kastanos, E. | en |
dc.contributor.author | Witzgall, R. | en |
dc.contributor.author | Bai, C. -X | en |
dc.contributor.author | Li, L. | en |
dc.contributor.author | Tsiokas, L. | en |
dc.contributor.author | Gretz, N. | en |
dc.contributor.author | Constantinou-Deltas, Constantinos D. | en |
dc.creator | Felekkis, Kyriacos N. | en |
dc.creator | Koupepidou, P. | en |
dc.creator | Kastanos, E. | en |
dc.creator | Witzgall, R. | en |
dc.creator | Bai, C. -X | en |
dc.creator | Li, L. | en |
dc.creator | Tsiokas, L. | en |
dc.creator | Gretz, N. | en |
dc.creator | Constantinou-Deltas, Constantinos D. | en |
dc.date.accessioned | 2019-11-04T12:50:33Z | |
dc.date.available | 2019-11-04T12:50:33Z | |
dc.date.issued | 2008 | |
dc.identifier.issn | 1471-2369 | |
dc.identifier.uri | http://gnosis.library.ucy.ac.cy/handle/7/53068 | |
dc.description.abstract | Background. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is characterized by the formation of multiple fluid-filled cysts that destroy the kidney architecture resulting in end-stage renal failure. Mutations in genes PKD1 and PKD2 account for nearly all cases of ADPKD. Increased cell proliferation is one of the key features of the disease. Several studies indicated that polycystin-1 regulates cellular proliferation through various signaling pathways, but little is known about the role played by polycystin-2, the product of PKD2. Recently, it was reported that as with polycystin-1, polycystin-2 can act as a negative regulator of cell growth by modulating the levels of the cyclin-dependent kinase inhibitor, p21 and the activity of the cyclin-dependent kinase 2, Cdk2. Methods. Here we utilized different kidney cell-lines expressing wild-type and mutant PKD2 as well as primary tubular epithelial cells isolated from a PKD transgenic rat to further explore the contribution of the p21/Cdk2 pathway in ADPKD proliferation. Results. Surprisingly, over-expression of wild-type PKD2 in renal cell lines failed to inactivate Cdk2 and consequently had no effect on cell proliferation. On the other hand, expression of mutated PKD2 augmented proliferation only in the primary tubular epithelial cells of a rat model but this was independent of the STAT-1/p21 pathway. On the contrary, multiple approaches revealed unequivocally that expression of the cyclin-dependent kinase inhibitor, p57KIP2, is downregulated, while p21 remains unchanged. This p57 reduction is accompanied by an increase in Cdk2 levels. Conclusion. Our results indicate the probable involvement of p57KIP2 on epithelial cell proliferation in ADPKD implicating a new mechanism for mutant polycystin-2 induced proliferation. Most importantly, contrary to previous studies, abnormal proliferation in cells expressing mutant polycystin-2 appears to be independent of STAT-1/p21. © 2008 Felekkis et al | en |
dc.description.abstract | licensee BioMed Central Ltd. | en |
dc.source | BMC Nephrology | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-51649086198&doi=10.1186%2f1471-2369-9-10&partnerID=40&md5=051198abf543378fd313cb2ca37eed42 | |
dc.subject | article | en |
dc.subject | human | en |
dc.subject | Humans | en |
dc.subject | kidney polycystic disease | en |
dc.subject | cell proliferation | en |
dc.subject | gene expression regulation | en |
dc.subject | nonhuman | en |
dc.subject | pathology | en |
dc.subject | signal transduction | en |
dc.subject | metabolism | en |
dc.subject | human cell | en |
dc.subject | gene expression | en |
dc.subject | Animals | en |
dc.subject | animal | en |
dc.subject | animal cell | en |
dc.subject | biosynthesis | en |
dc.subject | genetics | en |
dc.subject | physiology | en |
dc.subject | gene mutation | en |
dc.subject | gene overexpression | en |
dc.subject | protein p21 | en |
dc.subject | Epithelial Cells | en |
dc.subject | enzyme inhibition | en |
dc.subject | enzyme activation | en |
dc.subject | genetic transfection | en |
dc.subject | Animals, Genetically Modified | en |
dc.subject | transgenic animal | en |
dc.subject | amino acid substitution | en |
dc.subject | mutant protein | en |
dc.subject | Polycystic Kidney, Autosomal Dominant | en |
dc.subject | cell division | en |
dc.subject | autosomal dominant inheritance | en |
dc.subject | missense mutation | en |
dc.subject | Mutation, Missense | en |
dc.subject | polycystin | en |
dc.subject | polycystin 1 | en |
dc.subject | TRPP Cation Channels | en |
dc.subject | Transfection | en |
dc.subject | rat | en |
dc.subject | Rats | en |
dc.subject | hybrid protein | en |
dc.subject | Recombinant Fusion Proteins | en |
dc.subject | polycystin 2 | en |
dc.subject | Cdk2 protein, rat | en |
dc.subject | cell line | en |
dc.subject | cell membrane potential | en |
dc.subject | cell strain HEK293 | en |
dc.subject | cyclin dependent kinase 2 | en |
dc.subject | cyclin dependent kinase inhibitor 1C | en |
dc.subject | Cyclin-Dependent Kinase 2 | en |
dc.subject | Cyclin-Dependent Kinase Inhibitor p57 | en |
dc.subject | epithelium cell | en |
dc.subject | kidney tubule | en |
dc.subject | kidney tubule cell | en |
dc.subject | Kidney Tubules | en |
dc.subject | Membrane Potentials | en |
dc.subject | p21 activated kinase | en |
dc.subject | p21-Activated Kinases | en |
dc.subject | Pak1 protein, rat | en |
dc.subject | patch clamp | en |
dc.subject | Patch-Clamp Techniques | en |
dc.subject | point mutation | en |
dc.subject | polycystic kidney disease 2 protein | en |
dc.subject | protein p57 | en |
dc.subject | STAT1 protein | en |
dc.subject | Stat1 protein, rat | en |
dc.subject | STAT1 Transcription Factor | en |
dc.subject | transgenic rat | en |
dc.title | Mutant polycystin-2 induces proliferation in primary rat tubular epithelial cells in a STAT-1/p21-independent fashion accompanied instead by alterations in expression of p57KIP2 and Cdk2 | en |
dc.type | info:eu-repo/semantics/article | |
dc.identifier.doi | 10.1186/1471-2369-9-10 | |
dc.description.volume | 9 | |
dc.author.faculty | Σχολή Θετικών και Εφαρμοσμένων Επιστημών / Faculty of Pure and Applied Sciences | |
dc.author.department | Τμήμα Βιολογικών Επιστημών / Department of Biological Sciences | |
dc.type.uhtype | Article | en |
dc.description.notes | <p>Cited By :11</p> | en |
dc.source.abbreviation | BMC Nephrol. | en |
dc.contributor.orcid | Constantinou-Deltas, Constantinos D. [0000-0001-5549-9169] | |
dc.gnosis.orcid | 0000-0001-5549-9169 | |