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TGF-β1在AVP诱导的心肌成纤维细胞表型转化中的作用(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2012年第1期
页码:
7-11
栏目:
基础研究
出版日期:
2012-02-25

文章信息/Info

Title:
Role of transforming growth factor β1 in differentiation of cardiac fibroblasts induced by arginine vasopressin
作者:
范延红1; 董 辉2; 潘 庆3; 郭文怡1; 王海昌1
(第四军医大学西京医院：1.心血管内科，2.麻醉科，陕西 西安 710032；3.第二炮兵工程学院门诊部，陕西 西安 710000)
Author(s):
FAN Yan-hong1;  DONG Hui2;  PAN Qing3;  GUO Wen-yi1;  WANG Hai-chang1
(1.Department of Cardiology, 2.Department of Anesthesia, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China; 3.Outpatient Department, Second Artillery Engineering College, Xi’an 710025, Shaanxi, China)
关键词:
精氨酸加压素; 转化生长因子β1; 心肌成纤维细胞; 肌成纤维细胞; 转化
Keywords:
arginine vasopressin;  transforming growth factor β1;  cardiac fibroblasts;  myofibroblasts;  differentiation
分类号:
R542.2
DOI:
-
文献标识码:
A
摘要:
目的:探讨转化生长因子β1(TGF-β1)在精氨酸加压素(AVP)诱导的心肌成纤维细胞(CFs)向肌成纤维细胞(MFs)转化中的作用。方法： 用胰酶消化法分离培养SD仔鼠的CFs，将CFs分别与不同浓度的AVP、不同浓度的TGF-β1或添加了不同浓度的抗TGF-β1中和抗体的1×10-6 mmol/L AVP共同孵育48 h后，用3H-脯氨酸掺入法检测CFs胶原合成的功能，用Western blot检测CFs中平滑肌肌动蛋白α (α-SMA)的表达量，用ELISA法检测CFs中TGF-β1的合成。结果： AVP可浓度依赖性地诱导CFs的3H-脯氨酸掺入率和α-SMA的表达量增加，其中1×10-6 mmol/L AVP组CFs的3H-脯氨酸掺入率和α-SMA的表达量显著高于对照组(P<0.05)。AVP也可浓度依赖性地诱导CFs中内源性TGF-β1的合成增加，其中在1×10-6 mmol/L AVP刺激下，CFs合成显著增加的内源性TGF-β1刚好达到外源性TGF-β1诱导CFs向MFs转化所需要的剂量(>2 ng/ml)。抗TGF-β1中和抗体虽然能够显著抑制在10-6 mmol/L AVP诱导下CFs的3H-脯氨酸掺入率和α-SMA的表达量(P<0.05)，但却不能将其抑制到与对照组相近的水平(P<0.05)。结论： AVP刺激下CFs中内源性TGF-β1合成的增加可部分地介导AVP诱导的CFs向MFs转化。
Abstract:
AIM:To investigate the role of transforming growth factor β1 (TGF-β1) in the differentiation of cardiac fibroblasts (CFs) into myofibroblasts (MFs) induced by arginine vasopressin (AVP). METHODS: CFs were isolated by trypsin digestion method and co-incubated for 48 h with different concentrations of AVP, different concentrations of TGF-β1, or 1×10-6 mmol/L AVP supplemented with different concentrations of TGF-β1 neutralizing antibody, respectively. 3H proline incorporation was used to measure collagen synthesis, Western blot analysis was used to measure α-smooth muscle actin (α-SMA) expression, and ELISA was used to measure TGF-β1 secretion in CFs. RESULTS: AVP induced the increases of 3H proline incorporation and α-SMA expression dose dependently in CFs, and 1×10-6 mol/L AVP notably increased 3H proline incorporation and α-SMA expression compared with those in control group (P<0.05). AVP induced endogenous TGF-β1 secretion of CFs dose dependently, and the notably increased endogenous TGF-β1 induced by 1×10-6 mol/L AVP was well within the range for exogenous TGF-β1 to cause differentiation of CFs into MFs (>2 ng/ml). Although 1×10-6 mol/L AVP-induced increases of 3H proline incorporation and α-SMA expression could be notably inhibited by TGF-β1 neutralizing antibody (P<0.05), they were still higher than those in control group (P<0.05). CONCLUSION: AVP can induce differentiation of CFs into MFs partly through the increase of endogenous TGF-β1 synthesis.

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备注/Memo

备注/Memo:
收稿日期：2011-09-03.基金项目：国家自然科学基金项目资助(30800470) 作者简介：范延红，副主任医师，博士 Email：fanyh1@fmmu.edu.cn
更新日期/Last Update: 2012-02-14