MMP/TIMP balance is modulated in vitro by 15dPGJ2 in fetuses and placentas from diabetic rats

M.C. PUSTOVRH,; E. CAPOBIANCO,; N. MARTÍNEZ,; R. HIGA,; V. WHITE,; A. JAWERBAUM

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION.

Wiley-Blackwell

Lugar: Oxford-England; Año: 2009 vol. 39 p. 1082 - 1090

0014-2972

Background Maternal diabetes is associated with morphological placental abnormalities and foeto-placental impairments. These alterations are linked with a dysregulation of the activity of matrix metalloproteinases (MMPs). We investigated the action of 15deoxyD12,14 prostaglandin J2 (15dPGJ2), a natural ligand of the peroxisome proliferator activated receptor (PPAR) c, on MMP-2 and MMP-9 activities and tissue inhibitors of matrix metalloproteinases (TIMP) levels in foetuses and placentas from diabetic rats. Materials and methods Diabetes was induced in rat neonates by a single streptozotocin administration (90 mg kg)1 s.c.). At 13Æ5 days of gestation, foetal and placental homogenates were prepared for the determination of PPARc levels (western blot) and 15dPGJ2 concentration (enzyme-immunoassay), whereas the in vitro effect of 15dPGJ2 (2 lM) was evaluated on placental and foetal MMPs and TIMP activities (zymography and reverse zymography), nitrate ⁄ nitrite concentrations (Griess method) and thiobarbituric acid reactive substances (TBARS). Results PPARc was increased while 15dPGJ2 was decreased in placentas and foetuses from diabetic rats. 15dPGJ2 additions were able to reduce the high activities of MMP-2 and MMP-9 present in diabetic placental tissues. 15dPGJ2 additions reduced MMP-2 activity in control and diabetic foetuses. TIMP-3 levels were decreased in diabetic placentas and 15dPGJ2 was able to enhance them to control values. Nitrates ⁄ nitrites andTBARS, metabolites of MMPs activators, were increased in the diabetic placenta and reduced by 15dPGJ2. Conclusions This study demonstrates that 15dPGJ2 is a potent modulator of the balance between MMP activities and TIMP levels, which is needed in the correct formation and function of the placenta and foetal organs