Activin A is an autocrine activator of rat pancreatic stellate cells: potential therapeutic role of follistatin for pancreatic fibrosis
Activin A is an autocrine activator of rat pancreatic stellate cells: potential therapeutic role of follistatin for pancreatic fibrosis
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DOI：
10.1136/gut.52.10.1487
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发表时间：
2003-10-01
期刊：
影响因子：
24.5
通讯作者：
Sugano, K
中科院分区：
文献类型：
--
作者：
Ohnishi, N;Miyata, T;Sugano, K
背景与目的：探讨激活素A对大鼠胰腺星状细胞(PSCs)活化的影响。方法：采用胶原酶消化、Nycodenz梯度离心法分离大鼠胰腺星状细胞。用免疫印迹法检测PSCs的激活情况。逆转录-聚合酶链式反应(RT-PCR)、Western blotting和免疫细胞化学检测PSCs中激活素A受体的表达。RT-PCR检测激活素A和转化生长因子-β(TGF-β)mRNA的表达。用酶联免疫吸附试验检测激活素A和转化生长因子-β多肽的浓度。免疫细胞化学方法检测PSCs中激活素A肽的存在。结果：PSCs中存在激活素A受体I和IIa。PSCs表达激活素A并分泌激活素A，激活素A以剂量依赖方式促进PSC活化和胶原分泌。转化生长因子-β和激活素A相互促进PSCs的分泌和mRNA表达。结论：激活素A是PSCs的自分泌激活剂。卵泡刺激素通过阻断自分泌的激活素A，减少转化生长因子-β的表达和分泌，从而抑制PSC的活化和胶原分泌。
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.