Heparin induces alpha-smooth muscle actin expression in cultured fibroblasts and in granulation tissue myofibroblasts.
Heparin induces alpha-smooth muscle actin expression in cultured fibroblasts and in granulation tissue myofibroblasts.
复制标题
肝素诱导培养的成纤维细胞和肉芽组织肌成纤维细胞中α-平滑肌肌动蛋白的表达。
DOI：
--
复制
发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Giulio Gabbiani
中科院分区：
文献类型：
--
作者：
Alexis Desmoulière;Laura Rubbia;G. Grau;Giulio Gabbiani
背景
肝素可增加体内和体外平滑肌细胞中α-平滑肌肌动蛋白的表达。最近有人提出，成纤维细胞中α-平滑肌肌动蛋白的表达是肌成纤维细胞分化的标志。我们在体外和体内研究了肝素和四种非抗凝肝素衍生物对成纤维细胞表达α-平滑肌肌动蛋白的影响。
实验设计
对于体外实验，将肝素添加到不同的成纤维细胞培养物中 7 天。我们研究了细胞增殖和 α-平滑肌肌动蛋白及 mRNA 表达。对于体内研究，皮下植入充满 NaCl 或肿瘤坏死因子-α（不含或含非抗凝肝素）的渗透微型泵。 14 天后，对泵周围新积累的结缔组织进行处理，用于免疫荧光、电子显微镜和生化研究。
结果
在体外，肝素抑制增殖并增加α-平滑肌肌动蛋白和mRNA的表达。对同步细胞中[3H]胸苷掺入的分析表明，肝素产生了一系列表达α-平滑肌肌动蛋白的细胞。在体内，肿瘤坏死因子-α的局部应用导致典型肉芽组织的形成：免疫荧光显示，积累的成纤维细胞仅在存在肝素衍生物的情况下表达α-平滑肌肌动蛋白。在肿瘤坏死因子-α治疗的动物中，电子显微镜检查证实了肌成纤维细胞的存在，但α-平滑肌肌动蛋白仅在存在肝素衍生物的情况下在微丝束中表达。
结论
这些结果表明，肝素及其非抗凝衍生物在体外和体内影响成纤维细胞中α-平滑肌肌动蛋白的表达，并且这种效应可能与特定细胞亚群的选择有关。他们提出肝素在肉芽组织的形成和进化过程中可能发挥的作用。
BACKGROUND
Heparin increases alpha-smooth muscle actin expression in smooth muscle cells in vivo and in vitro. It has been recently suggested that alpha-smooth muscle actin expression in fibroblasts is a marker of myofibroblastic differentiation. We have examined the effect of heparin and of four nonanticoagulant heparin derivatives on alpha-smooth muscle actin expression by fibroblasts in vitro and in vivo.
EXPERIMENTAL DESIGN
For in vitro experiments, heparin was added for 7 days to different fibroblastic cultures. We studied cell proliferation and alpha-smooth muscle actin protein and mRNA expression. For in vivo studies, osmotic minipumps filled with NaCl or tumor necrosis factor-alpha without or with nonanticoagulant heparin were implanted subcutaneously. After 14 days, newly accumulated connective tissues around the pumps were processed for immunofluorescence and electron microscopic and biochemical studies.
RESULTS
In vitro, heparin inhibited proliferation and increased the expression of alpha-smooth muscle actin protein and mRNA. Analysis of [3H]thymidine incorporation in synchronized cells suggested that heparin produces a selection of alpha-smooth muscle actin expressing cells. In vivo, the local application of tumor necrosis factor-alpha resulted in formation of a typical granulation tissue: immunofluorescence showed that accumulated fibroblastic cells express alpha-smooth muscle actin only in the presence of heparin derivatives. In tumor necrosis factor-alpha treated animals, electron microscopic examination established the presence of myofibroblasts, but alpha-smooth muscle actin was expressed in microfilament bundles only in the presence of heparin derivatives.
CONCLUSIONS
These results show that heparin and its nonanticoagulant derivatives influence the expression of alpha-smooth muscle actin in fibroblastic cells both in vitro and in vivo and that this effect is probably related to the selection of a particular cell subpopulation. They suggest a possible role for heparin during the formation and evolution of granulation tissue.