激活素A是大鼠胰腺星状细胞的自分泌激活剂：卵泡抑素对胰腺纤维化的潜在治疗作用。
Activin A is an autocrine activator of rat pancreatic stellate cells: potential therapeutic role of follistatin for pancreatic fibrosis.
作者信息
Ohnishi N, Miyata T, Ohnishi H, Yasuda H, Tamada K, Ueda N, Mashima H, Sugano K
机构信息
Department of Internal Medicine, Jichi Medical School, Tochigi, Japan.
出版信息
Gut. 2003 Oct;52(10):1487-93. doi: 10.1136/gut.52.10.1487.
BACKGROUND AND AIM
The present study was conducted to examine the effect of activin A on activation of rat pancreatic stellate cells (PSCs).
METHODS
PSCs were prepared from rat pancreas using collagenase digestion and centrifugation with Nycodenz gradient. Activation of PSCs was examined by determining smooth muscle actin expression with western blotting. The presence of activin A receptors in PSCs was investigated by reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and immunocytochemistry. Expression of activin A and transforming growth factor beta (TGF-beta) mRNA was examined by RT-PCR. Activin A and TGF-beta peptide concentrations were examined with ELISA. Existence of activin A peptide in PSCs was investigated by immunocytochemistry. Collagen secretion was determined by Sirius red dye binding.
RESULTS
Activin A receptors I and IIa were present in PSCs. PSCs expressed activin A mRNA and secreted activin A. Activin A enhanced PSC activation and collagen secretion in a dose dependent manner. TGF-beta and activin A increased each other's secretion and mRNA expression of PSCs. Follistatin decreased TGF-beta mRNA expression and TGF-beta secretion of PSCs, and inhibited both PSC activation and collagen secretion.
CONCLUSION
Activin A is an autocrine activator of PSCs. Follistatin can inhibit PSC activation and collagen secretion by blocking autocrined activin A and decreasing TGF-beta expression and secretion of PSCs.
背景与目的
本研究旨在探讨激活素A对大鼠胰腺星状细胞（PSC）激活的影响。
方法
采用胶原酶消化法及Nycodenz梯度离心法从大鼠胰腺制备PSC。通过蛋白质印迹法检测平滑肌肌动蛋白表达来检测PSC的激活情况。采用逆转录-聚合酶链反应（RT-PCR）、蛋白质印迹法和免疫细胞化学法研究PSC中激活素A受体的存在情况。通过RT-PCR检测激活素A和转化生长因子β（TGF-β）mRNA的表达。采用酶联免疫吸附测定法检测激活素A和TGF-β肽浓度。通过免疫细胞化学法研究PSC中激活素A肽的存在情况。采用天狼星红染料结合法测定胶原蛋白分泌。
结果
PSC中存在激活素A受体I和IIa。PSC表达激活素A mRNA并分泌激活素A。激活素A以剂量依赖方式增强PSC激活和胶原蛋白分泌。TGF-β和激活素A相互增加对方在PSC中的分泌及mRNA表达。卵泡抑素降低PSC的TGF-β mRNA表达和TGF-β分泌，并抑制PSC激活和胶原蛋白分泌。
结论
激活素A是PSC的自分泌激活剂。卵泡抑素可通过阻断自分泌的激活素A并降低PSC的TGF-β表达及分泌来抑制PSC激活和胶原蛋白分泌。
Zotero 插件