الفهرس يوجد فقط 14 صفحة متاحة للعرض العام
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المستخلص
Pancreatic stellate cells (PSCs) produce ECM after stimulation with profibrogenic cytokines including TGF-β1. It has been reported that TGF-β1 is the key regulating factor of fibrosis. Modulation of TGF-β1 level may be the therapeutic target for the prevention of CP.
Recent studies have shown that the RAS is present intrinsically in the pancreas and that its level is enhanced during AP and CP in experimental animals, suggesting the role of the RAS in pancreatic diseases.
The angiotensin II (Ang II)-AT1 receptor pathway is shown to be implicated in fibrosis of critical organs, including the pancreas, heart, kidney, and liver. Ang II is considered the major bioactive effector of the RAS, eliciting a variety of biological actions spanning the diverse roles of the RAS in homeostasis of many organ systems. However, Ang II is more than just a vasoconstrictor, and has trophic effects independent of its haemodynamic actions. More recently the role of Ang II in hypertrophy has been recognized. It also acts as a pro-inflammatory, pro-fibrotic and pro-thrombotic agent. It has direct effects on the pancreas including stimulation of pro-fibrotic cytokines and their receptors as TGF-β1, activation of angiogenic cytokines and related molecules and promoting macrophage recruitment and infiltration, partly via increasing expression of the MCP-1.
Recent in-vivo and in-vitro studies showed that Ang II acts as a fibrogenic mediator via HSCs in the liver. In fact, activated human and rat HSCs express AT1 receptors, and Ang II induces proliferation and collagen synthesis in HSCs through the AT1 receptors. Activated PSCs also express AT1 receptors and the Ang II-AT1 receptor pathway has been reported to play an important role in pancreatic fibrogenesis.