Failure of angiotensin II and insulin to stimulate transforming growth factor-beta1. Release from cultured bovine retinal pericytes.
BACKGROUND
Activation of the renin-angiotensin system (RAS) may induce cardiovascular and renal fibrosis in hypertension and diabetes. This fibrogenic effect is mainly mediated by Transforming Growth Factor-B1 (TGF-B1), a multifunctional citokyne released by endothelial, vascular smooth muscle and renal mesangial cells, that is able to increase extracellular matrix deposition. Retinal capillary pericytes have functions similar to those of mesangial cells, including ability to synthesize and release TGF-B1 and produce extracellular matrix. An intraocular RAS was described in the human eye and may produce effects similar to those observed in the heart and kidney, which could be mediated by TGF-B1. In particular, TGF-B1 might be involved in thickening of the capillary basement membrane in diabetic microangiopathy. We therefore aimed at evaluating the possible effects of Angiotensin-II on TGF-B1 secretion by cultured retinal pericytes (BRP).


METHODS
BRP cultures were incubated with Angiotensin-II or insulin (known to play a permissive effect on TGF-B1 release from mesangial cells) or Angiotensin-II + insulin at final concentrations of 10-10, 10-8, 10-6, 10-4 mol/L.


RESULTS
Baseline TGF-B1 concentrations in the supernatants of pericyte cultures were 6 139 +/- 1 919 pg/mL/106 cells; no changes of TGF-B1 concentrations resulted from adding increasing amounts of Ang II, insulin or both.


CONCLUSIONS
Though confirming that cultured bovine retinal pericytes spontaneously release TGF-B1, Angiotensin-II did not produce any stimulatory effects of in our experimental system
Limone
P
P
Department of Internal Medicine, University of Torino, Italy. paolopiero.limone@unito.it
Berardi
C
C
Pomero
F
F
Del Rizzo
P
P
Allione
A
A
Beltramo
E
E
D'alu
F
F
Ponte
E
E
Pellissetto
C
C
Lacaria
A
A
Barberis
A M
AM
Porta
M
M
D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D007328:Insulin / Q000494:pharmacology*; D020286:Pericytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D007328:Insulin; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II