可溶性因子调节腹主动脉瘤中胶原蛋白基因表达的变化。

Soluble factors modulate changes in collagen gene expression in abdominal aortic aneurysms.

作者信息

Minion D J, Wang Y, Lynch T G, Fox I J, Prorok G D, Baxter B T

机构信息

Department of Surgery, University of Nebraska Medical Center, Omaha 68198.

出版信息

Surgery. 1993 Aug;114(2):252-6; discussion 256-7.

PMID:8342129

Abstract

BACKGROUND

Although increased procollagen gene expression and synthesis have been implicated in the progression of abdominal aortic aneurysms (AAA), factors modulating this change have not been identified. Furthermore, it is not known whether the increase in AAA procollagen expression is specific to this disease or also occurs in tissue affected by atherosclerotic occlusive disease (AOD). If paracrine rather than autocrine factors are responsible for increased gene expression in AAA, this effect should be transferable to target smooth muscle cells through conditioned media. Our objectives were to determine 1 alpha (I) procollagen messenger RNA levels in AOD tissue compared with normal and AAA and to determine whether differences noted in tissue procollagen gene expression could be transferred through conditioned media from normal, AOD, and AAA tissues to target smooth muscle cells in primary culture.

METHODS

Normal, AOD, and AAA tissue was used for tissue RNA extraction or was minced and washed with serum-free media (4 degrees C) x 30 minutes and the media applied to human aortic smooth muscle cells (SMC) in primary culture for 36 hours. Total RNA from tissue and SMC exposed to conditioned media was analyzed by Northern and dot blot analysis for 1 alpha (I) procollagen.

RESULTS

Relative tissue 1 alpha (I) procollagen levels were not increased in AOD (0.23 +/- 0.05) as compared with normal (0.17 +/- 0.03); both were decreased compared with AAA (0.53 +/- 0.07; p < 0.01). The 1 alpha (I) procollagen levels in SMC exposed to conditioned media from AAA (1.73 +/- 0.15) were increased (p < 0.05) compared with AOD (1.10 +/- 0.12) and normal (1.16 +/- 0.16).

CONCLUSIONS

There is no increase in tissue AOD procollagen gene expression. The ability to transfer the same relative patterns of gene expression from tissue to target SMC with conditioned media suggests that paracrine, rather than autocrine, factors modulate procollagen expression in AAA tissues.

摘要

背景

尽管前胶原基因表达和合成增加与腹主动脉瘤（AAA）的进展有关，但调节这种变化的因素尚未明确。此外，尚不清楚AAA中前胶原表达的增加是该疾病所特有的，还是也发生在受动脉粥样硬化闭塞性疾病（AOD）影响的组织中。如果旁分泌而非自分泌因素导致AAA中基因表达增加，那么这种效应应该可以通过条件培养基传递给靶平滑肌细胞。我们的目标是确定与正常组织和AAA组织相比，AOD组织中1α（I）前胶原信使核糖核酸水平，并确定组织前胶原基因表达中观察到的差异是否可以通过来自正常、AOD和AAA组织的条件培养基传递给原代培养的靶平滑肌细胞。

方法

正常、AOD和AAA组织用于提取组织RNA，或将其切碎并用无血清培养基（4℃）洗涤30分钟，然后将培养基应用于原代培养的人主动脉平滑肌细胞（SMC）36小时。通过Northern印迹和斑点印迹分析，对暴露于条件培养基的组织和SMC中的总RNA进行1α（I）前胶原分析。

结果

与正常组织（0.17±0.03）相比，AOD组织（0.23±0.05）中相对组织1α（I）前胶原水平没有增加；与AAA组织（0.53±0.07；p<0.01）相比，两者均降低。与AOD（1.10±0.12）和正常组织（1.16±0.16）相比，暴露于AAA条件培养基的SMC中1α（I）前胶原水平增加（p<0.05）。