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Decreased response to epidermal growth factor during cellular senescence in cultured human microvascular endothelial cells
Author(s) -
Matsuda Takao,
Okamura Kazuki,
Sato Yasufumi,
Morimoto Akio,
Ono Mayumi,
Kohno Kimitoshi,
Kuwano Michihiko
Publication year - 1992
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041500311
Subject(s) - epidermal growth factor , biology , receptor , in vitro , plasminogen activator , senescence , endocrinology , microbiology and biotechnology , downregulation and upregulation , cell culture , growth factor , endothelial stem cell , medicine , biochemistry , genetics , gene
We have previously demonstrated that epidermal growth factor (EGF) induces cell migration, tissue‐type plasminogen activator synthesis, as well as tubular formation in microvascular endothelial cells from human omental tissue. In this study, we compared the responsiveness to EGF of late passaged (senescent) human omental microvascular endothelial (HOME) cells with that of early passaged (young) HOME cells. We have employed HOME cells derived from surgically resected omental samples from 14 patients. EGF stimulated cell migration significantly more in the young cells than in the senescent cells during serial cultivation (aging) in vitro. Scatchard analysis demonstrated that the number for both high and low affinity receptors for EGF in HOME cells was decreased dramatically during serial cultivation. The expression of EGF receptor mRNA was also decreased in the senescent HOME cells. Treatment of HOME cells with EGF significantly increased cellular mRNA levels of tissue‐type plasminogen activator, and two protooncogenes, c‐fos and c‐myc, in young HOME cells, but not in senescent HOME cells. Thus HOME cells aged in vitro show a decreased responsiveness to EGF, resulting in decreased migration of human endothelial cells. The serial cultivation of human endothelial cells in vitro may downregulate EGF receptor and decrease responsiveness to exogenous EGF, a potent angiogenic factor.