Captopril reverses high-glucose-induced growth effects on LLC-PK1 cells partly by decreasing transforming growth factor-beta receptor protein expressions.
Transforming growth factor beta (TGF-beta) may be important in the pathogenesis of diabetic nephropathy, and captopril is effective in treating this disorder. However, the mechanisms of this therapeutic effect as related to TGF-beta and its receptors are not known. Thus, the effects of captopril on cellular growth, TGF-beta 1, and TGF-beta receptors were studied in LLC-PK1 cells cultured in normal (11 mM) or high glucose (27.5 mM). This study found that glucose dose-dependently inhibited cellular mitogenesis while inducing hypertrophy in these cells at 72 h of culture, concomitantly with enhanced TGF-beta 1 messenger RNA (mRNA) and TGF-beta receptor Types I and II protein expressions. Captopril dose-dependently (0.1 to 10 mM) increased cellular mitogenesis and inhibited hypertrophy in these cells. Moreover, captopril also decreased TGF-beta receptor Types I and II protein expressions dose-dependently. However, TGF-beta 1 mRNA was not affected by captopril. It was concluded that high glucose decreased cellular mitogenesis while increasing hypertrophy concomitantly with increased TGF-beta 1 mRNA and TGF-beta receptors in LLC-PK1 cells. Captopril can reverse high-glucose-induced growth effects by decreasing TGF-beta receptor protein expressions.
Guh
J Y
JY
Department of Internal Medicine, Kaohsiung Medical College, Taiwan, Republic of China.
Yang
M L
ML
Yang
Y L
YL
Chang
C C
CC
Chuang
L Y
LY
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D003928:Diabetic Nephropathies / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects*; D018374:LLC-PK1 Cells; D012333:RNA, Messenger / Q000096:biosynthesis; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D013552:Swine; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics
D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D002216:Captopril; D005947:Glucose