ArticleBMC nephrology2008
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.
Article in BMC nephrology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- High CD133 expression in proximal tubular cells in diabetic kidney disease: good or bad?Journal of translational medicine · 2024Article
- Metabolic Reprogramming and Reconstruction: Integration of Experimental and Computational Studies to Set the Path Forward in ADPKD.Frontiers in medicine · 2021Review
- Cellular Senescence: A New Player in Kidney Injury.Hypertension (Dallas, Tex. : 1979) · 2020Review
- An Overview of In Vivo and In Vitro Models for Autosomal Dominant Polycystic Kidney Disease: A Journey from 3D-Cysts to Mini-Pigs.International journal of molecular sciences · 2020Review
- Role of cyclin-dependent kinase 2 in the progression of mouse juvenile cystic kidney disease.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Renal expression of JAK2 is high in polycystic kidney disease and its inhibition reduces cystogenesis.Scientific reports · 2019Article
- Casein kinase 1ε and 1α as novel players in polycystic kidney disease and mechanistic targets for (R)-roscovitine and (S)-CR8.American journal of physiology. Renal physiology · 2018Article
- Efficient Conversion of Spermatogonial Stem Cells to Phenotypic and Functional Dopaminergic Neurons via the PI3K/Akt and P21/Smurf2/Nolz1 Pathway.Molecular neurobiology · 2015Article
- The hallmarks of cancer: relevance to the pathogenesis of polycystic kidney disease.Nature reviews. Nephrology · 2015Review
- Fibroblast growth factor 4 is required but not sufficient for the astrocyte dedifferentiation.Molecular neurobiology · 2014Article
- Review
- STAT1 is required for redifferentiation during Madin-Darby canine kidney tubulogenesis.Molecular biology of the cell · 2010Article
- Cyst formation in the PKD2 (1-703) transgenic rat precedes deregulation of proliferation-related pathways.BMC nephrology · 2010Article
- Down-regulation of Pkd2 by siRNAs suppresses cell-cell adhesion in the mouse melanoma cells.Molecular biology reports · 2010Article
- Autosomal dominant polycystic kidney disease: the last 3 years.Kidney international · 2009Review
- Kidney: polycystic kidney disease.Wiley interdisciplinary reviews. Developmental biologyReview
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAutosomal 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.
methodsHere 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.
resultsSurprisingly, 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.
conclusionOur 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.
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