1. Protective role of angiotensin II type 2 receptor signaling in a mouse model of pancreatic fibrosis
- Author
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Ulmasov, Barbara, Xu, Zekuan, Tetri, Laura H., Inagami, Tadashi, and Neuschwander-Tetri, Brent A.
- Subjects
Pancreatitis -- Development and progression ,Transforming growth factors -- Properties ,Renin-angiotensin system -- Properties ,Angiotensin -- Receptors ,Angiotensin -- Properties ,Biological sciences - Abstract
The renin-angiotensin system contributes to pathological processes in a variety of organs. In the pancreas, blocking the angiotensin II (AII) type 1 receptor (AT1) attenuates pancreatic fibrogenesis in animal models of pancreatitis. Because the role of the AII type 2 receptor (AT2) in modulating pancreatic injury is unknown we investigated the role of AT2 in pancreatic injury and fibrosis. Pancreatic fibrosis was induced by repetitive cerulein administration in C57BL/6 wild-type (WT) or AT2-deficient (AT2-/-) mice and assessed by morphology and gene expression at 10 days. There was no difference between WT and AT2-/- mice in the degree of acute pancreatic injury as assessed by amylase release at 9 and 12 h and by histological examination of the pancreas at 12 h. In contrast, parenchymal atrophy and fibrosis were more pronounced in AT2-/- mice compared with WT mice at 10 days. Fibrosis was accompanied by activation of pancreatic stellate cells (PSC) evaluated by Western blot analysis for s-smooth muscle actin and by imrnunocytochemistry; PSC activation was further increased in AT2-/- mice compared with WT mice. The level of pancreatic transforming growth factor-[beta]1 mRNA and protein after repetitive cerulein treatment was higher in AT2-/- mice than in WT mice. Our results demonstrate that, in contrast to AT1 receptor signaling, AT2 receptor signaling modulates protective antifibrogenic effects in a mouse model of cerulein-induced pancreatic fibrogenesis. We propose that the effects of AII on injury-induced pancreatic fibrosis may be determined by the balance between AT1 and AT2 receptor signaling. renin-angiotensin system; transforming growth factor-[beta]1; pancreatitis
- Published
- 2009