Essential role(s) of the intrarenal renin-angiotensin system in transforming growth factor-beta1 gene expression and induction of hypertrophy of rat kidney proximal tubular cells in high glucose.
These studies investigated the question of whether the intrarenal renin-angiotensin system (RAS) is essential for transforming growth factor-beta1 (TGF-beta1) gene expression and induction of hypertrophy of renal proximal tubular cells in high glucose in vitro. Antisense and sense angiotensinogen (ANG) cDNAs were stably transfected into rat immortalized renal proximal tubular cells (IRPTC). ANG secretion from rat IRPTC was quantified by a specific RIA for rat ANG. Cellular ANG, TGF-beta1, and collagen alpha1 (type IV) mRNA levels were determined by Northern blot analysis or by reverse transcriptase-PCR assay. Hypertrophy of IRPTC was analyzed by Western blotting of cellular p27(Kip1) protein, flow cytometry, and cellular protein assay. The results showed that stable transfer of antisense ANG cDNA into IRPTC suppressed the basal TGF-beta1 and collagen alpha1 (type IV) mRNA expression and blocked the stimulatory effect of high glucose (i.e., 25 mM) on TGF-beta1 and collagen alpha1 (type IV) mRNA expression and induction of IRPTC hypertrophy. In contrast, stable transfer of sense ANG cDNA into IRPTC had no significant effect on these parameters. These data demonstrate that local intrarenal RAS activation is essential for TGF-beta1 gene expression and induction of hypertrophy of renal proximal tubular cells in high glucose.
Zhang
Shao-Ling
SL
Université de Montréal, *Centre hospitalier de l'Université de Montréal-Hôtel-Dieu and Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada; Harvard Medical School, Massachusetts General Hospital, Pediatric Nephrology Unit, Boston, Massachusetts.
To
Catherine
C
Université de Montréal, *Centre hospitalier de l'Université de Montréal-Hôtel-Dieu and Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada; Harvard Medical School, Massachusetts General Hospital, Pediatric Nephrology Unit, Boston, Massachusetts.
Chen
Xing
X
Université de Montréal, *Centre hospitalier de l'Université de Montréal-Hôtel-Dieu and Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada; Harvard Medical School, Massachusetts General Hospital, Pediatric Nephrology Unit, Boston, Massachusetts.
Filep
Janos G
JG
Université de Montréal, *Centre hospitalier de l'Université de Montréal-Hôtel-Dieu and Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada; Harvard Medical School, Massachusetts General Hospital, Pediatric Nephrology Unit, Boston, Massachusetts.
Tang
Shiow-Shih
SS
Université de Montréal, *Centre hospitalier de l'Université de Montréal-Hôtel-Dieu and Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada; Harvard Medical School, Massachusetts General Hospital, Pediatric Nephrology Unit, Boston, Massachusetts.
Ingelfinger
Julie R
JR
Université de Montréal, *Centre hospitalier de l'Université de Montréal-Hôtel-Dieu and Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada; Harvard Medical School, Massachusetts General Hospital, Pediatric Nephrology Unit, Boston, Massachusetts.
Chan
John S D
JSD
Université de Montréal, *Centre hospitalier de l'Université de Montréal-Hôtel-Dieu and Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada; Harvard Medical School, Massachusetts General Hospital, Pediatric Nephrology Unit, Boston, Massachusetts.
D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D024141:Collagen Type IV / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000502:physiology*; D005947:Glucose / Q000008:administration & dosage* / Q000494:pharmacology; D006984:Hypertrophy; D007668:Kidney / Q000187:drug effects* / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012084:Renin-Angiotensin System / Q000502:physiology*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
D024141:Collagen Type IV; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000808:Angiotensinogen; D005947:Glucose