Interaction between high glucose and TGF-beta in cell cycle protein regulations in MDCK cells.
Transforming growth factor-beta (TGF-beta) may mediate high glucose effects in renal cells. Thus, Madin-Darby canine kidney cells were studied for the modulation of cell cycle regulatory proteins by high glucose (27.5 mM) and TGF-beta1. We showed that unlike other renal cells, TGF-beta1 mRNA and its bioactivity were not induced by high-glucose culture. Furthermore, high glucose per se increased cellular proliferation without alterations in cell size. High glucose also increased the percentage of cells in the G2/M phase while decreasing cells in the G0/G1 phase of the cell cycle. In contrast, TGF-beta1 dose dependently (1 to 4 ng/ml) decreased cellular mitogenesis while increasing hypertrophy in the cells, especially in the presence of high glucose. TGF-beta1 also increased the percentage of cells arrested in the G0/G1 phase while decreasing cells in the G2/M phase of the cell cycle. Regarding two of the cell cycle regulatory proteins, high glucose increased cdc2 kinase activity and retinoblastoma protein (pRb) phosphorylation. In contrast, TGF-beta1 decreased cdc2 kinase activity and pRb phosphorylation, especially in the presence of high glucose. Additionally, glucose dose dependently (5.5, 16.5, 27.5, and 38.5 mM) increased type I and II TGF-beta receptor protein expression. In conclusion, changes in cdc2 kinase activity and pRb phosphorylation were correlated with high glucose and TGF-beta1-induced growth effects in a cell cycle-dependent manner in the Madin-Darby canine kidney cells. Furthermore, high glucose may potentiate TGF-beta1-induced effects by enhancing TGF-beta receptor protein expression.
Yang
Y L
YL
Department of Biochemistry, Kaohsiung Medical College, Taiwan, Republic of China.
Guh
J Y
JY
Yang
M L
ML
Lai
Y H
YH
Tsai
J H
JH
Hung
W C
WC
Chang
C C
CC
Chuang
L Y
LY
D000818:Animals; D016203:CDC2 Protein Kinase / Q000032:analysis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D007684:Kidney Tubules / Q000737:chemistry / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010770:Phosphotransferases / Q000187:drug effects / Q000378:metabolism; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis / Q000187:drug effects; D016160:Retinoblastoma Protein / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000494:pharmacology
D011506:Proteins; D018125:Receptors, Transforming Growth Factor beta; D016160:Retinoblastoma Protein; D016212:Transforming Growth Factor beta; D004247:DNA; D010770:Phosphotransferases; D016203:CDC2 Protein Kinase; D005947:Glucose; D013936:Thymidine