Effects of high dose retinoic acid on TGF-β2 expression during pancreatic organogenesis

Abstract

The aim of this study was to investigate the effects of excess all-trans retinoic acid, a vitamin A metabolite, on pancreatic organogenesis and TGF-beta2 expression during prenatal development in rats. First group of animals used as control while a single dose of 60 mg/kg all-trans retinoic acid was ingested by the mothers, at day 8 of gestation (before the neurulation period) in group II and at day 12 of gestation (after the neurulation period) in group III, and all embryos were sacrificed at day 18 of gestation. TGF-beta2 expression was detected in the capsule, acini and Langerhans islets in the control group. In the pancreas of group II, dilatation and congestion of interlobular vessels were observed. Langerhans islet structures were completely absent. Moreover acinar TGF-beta2 immune reactivity was not determined. In group III, acinar expression of TGF-beta2 in acid was similar to that in the controls but their Langerhans islets TGF-beta2 immune reactivity was significantly less than the controls. In view of the present findings we suggest that TGF-beta2 plays important role in pancreatic morphogenesis and administration of excess all-trans retinoic acid before neurulation inhibit TGF-beta2 expression disrupted pancreatic morphogenesis particularly Langerhans islets. However, its administration after neurulation had less adverse affect on pancreatic organogenesis and TGF-beta2 immune reactivity.

Retinoid and TGF-β Families: Crosstalk in Development, Neoplasia, Immunity, and Tissue Repair

“…In addition, TGF-β2 is required for the development of pancreatic and cerebral cortex; administration of excess ATRA before neurulation inhibits TGF-β2 expression in pancreas and brain and disrupts morphogenesis of pancreas and cerebral cotex 24,25 . TGF-β3 is required for chondrocyte differentiation, which is suppressed by ATRA.…”

Transforming growth factor β2 is negatively regulated by endogenous retinoic acid during early heart morphogenesis

“…Developmental events linked to RA‐regulated TGFβ signaling include the inner ear (Butts et al. 2005) and pancreas (Colakoglu et al. 2006).…”

“…It is well known that in many cells RA regulates TGFb signaling (Mahmood et al 1992(Mahmood et al , 1995Roberts & Sporn 1992a;Salbert et al 1993;Han et al 1997;Imai et al 1997;Yoshizawa et al 1998;Koli et al 2001;Walkley et al 2007), with TGFb2 being the most sensitive isoform to tissue retinoid levels . Developmental events linked to RA-regulated TGFb signaling include the inner ear (Butts et al 2005) and pancreas (Colakoglu et al 2006). Inhibition of TGFb signaling by endogenous RA is required for mouse lung development (Chen et al 2007).…”

Human Aldehyde Oxidase 1 Interacts with ATP-binding Cassette Transporter-1 and Modulates its Activity in Hepatocytes

“…Sigruener A et al AOX1 Associates with ABCA1 … Horm Metab Res 2007; 39: 781 -789 ferent cofactors [20] . Moreover, RA is an important signaling molecule implicated in mesenchymal / epithelial interactions in pancreatic development [21] . AOX1 is highly expressed in normal acinar cells of human pancreas.…”