Effects of CK2 inhibition in cultured fibroblasts from Type 1 Diabetic patients with or without nephropathy.
CK2 is a multifunctional, pleiotropic protein kinase involved in the regulation of cell proliferation and survival. Since fibroblasts from Type 1 Diabetes patients (T1DM) with Nephropathy exhibit increased proliferation, we studied cell viability, basal CK2 expression and activity, and response to specific CK2 inhibitors TBB (4,5,6,7-tetrabenzotriazole) and CX4945, in fibroblasts from T1DM patients either with (T1DM+) or without (T1DM-) Nephropathy, and from healthy controls (N). We tested expression and phosphorylation of CK2-specific molecular targets. In untreated fibroblasts from T1DM+, the cell viability was higher than in both N and T1DM-. CK2 inhibitors significantly reduced cell viability in all groups, but more promptly and with a larger effect in T1DM+. Differences in CK2-dependent phosphorylation sites were detected. In conclusion, our results unveil a higher dependence of T1DM+ cells on CK2 for their survival, despite a similar expression and a lower activity of this kinase compared with those of normal cells.
a Department of Medicine and.
Elisabetta
E
Iori
b Department of Biomedical Sciences , University of Padova , Padova , Italy , and.
Maria
M
Ruzzene
b Department of Biomedical Sciences , University of Padova , Padova , Italy , and.
Sofia
S
Zanin
a Department of Medicine and.
Stefano
S
Sbrignadello
b Department of Biomedical Sciences , University of Padova , Padova , Italy , and.|c Venetian Institute of Molecular Medicine , Padova , Italy.
Lorenzo Alberto
LA
Pinna
a Department of Medicine and.
Paolo
P
Tessari
D000328:Adult; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009287:Naphthyridines / Q000494:pharmacology; D010619:Phenazines; D047428:Protein Kinase Inhibitors / Q000494:pharmacology
D009287:Naphthyridines; D010619:Phenazines; D047428:Protein Kinase Inhibitors; C555142:silmitasertib; D047390:Casein Kinase II
CK2; Type 1 Diabetes; diabetic nephropathy; skin fibroblast cultures