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Cell cycle inhibitors (p27Kip1 and p21CIP1) cause hypertrophy in LLC-PK1 cells
- Source :
- Kidney International. 56(2):494-501
- Publication Year :
- 1999
- Publisher :
- Elsevier BV, 1999.
-
Abstract
- Cell cycle inhibitors (p27 Kip1 and p21 CIP1 ) cause hypertrophy in LLC-PK 1 cells. Background Angiotensin II has been reported to induce renal tubular hypertrophy, but the mechanisms of this hypertrophy are not well known. We evaluated the roles of cyclin-dependent kinase (CDK) inhibitors in renal tubular hypertrophy. Methods To elucidate whether CDK inhibitors cause renal tubular hypertrophy, we produced adenovirus vectors containing coding sequences of the CDK inhibitors p27 Kip1 (AxCAp27), p21 CIP1 (AxCAp21), and p16 INK4 (AxCAp16), and we investigated the effect of these gene transfers on epidermal growth factor (EGF)-induced proliferation in LLC-PK 1 cells. We evaluated the cell cycle and hypertrophy by measurements of the [ 3 H]-leucine and [ 3 H]-thymidine incorporation, the protein:DNA ratio, flow cytometry, and CDK4 and CDK2 kinase assays. Results AxCAp27 and AxCAp21 caused significant increases in [ 3 H]-leucine incorporation and the protein:DNA ratio but did not change the [ 3 H]-thymidine incorporation. Conversely, AxCAp16 inhibited EGF-stimulated [ 3 H]-thymidine incorporation but did not change the [ 3 H]-leucine incorporation. AxCAp27, AxCAp21, and AxCAp16 all inhibited EGF-stimulated CDK4 kinase activity (to 15.6, 14.1, and 21.9% of control, respectively). Forward light-scatter analysis demonstrated that AxCAp27 and AxCAp21 increased the cell size but that AxCAp16 effected no change in cell size. Conclusion These findings suggest that p27 Kip1 and p21 CIP1 may play an important role in hypertrophy of renal tubule cells by reducing pRb phosphorylation. On the other hand, p16 INK4 was not found to cause hypertrophic changes in EGF-treated LLC-PK 1 cells.
- Subjects :
- Swine
Renal Hypertrophy
Cell Cycle Proteins
Muscle hypertrophy
cyclin-dependent kinase inhibitors
CDC2-CDC28 Kinases
Vasoconstrictor Agents
Enzyme Inhibitors
biology
Kinase
phosphorylation
Angiotensin II
adenovirus
Cell cycle
Cyclin-Dependent Kinases
Nephrology
Kidney Diseases
Microtubule-Associated Proteins
Cyclin-Dependent Kinase Inhibitor p27
Cyclin-Dependent Kinase Inhibitor p21
Gene Expression Regulation, Viral
medicine.medical_specialty
CDK4
Genetic Vectors
Protein Serine-Threonine Kinases
Tritium
Gene Expression Regulation, Enzymologic
Adenoviridae
Cyclin-dependent kinase
Cyclins
Proto-Oncogene Proteins
Internal medicine
medicine
Animals
Kinase activity
Cyclin-Dependent Kinase Inhibitor p16
Cell Size
Cyclin-Dependent Kinase Inhibitor p15
renal hypertrophy
Cyclin-dependent kinase 4
urogenital system
Tumor Suppressor Proteins
Cyclin-Dependent Kinase 2
Cyclin-dependent kinase 2
Cyclin-Dependent Kinase 4
Hypertrophy
beta-Galactosidase
Molecular biology
Endocrinology
biology.protein
LLC-PK1 Cells
Carrier Proteins
Subjects
Details
- ISSN :
- 00852538
- Volume :
- 56
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Kidney International
- Accession number :
- edsair.doi.dedup.....cb24c844b357533f943d0e1c0a55f352
- Full Text :
- https://doi.org/10.1046/j.1523-1755.1999.00568.x