Project: Research project

Project Details


Respiratory epithelia are one of vitamin A-targeted tissues. In vitamin A
deficiency, the epithelium changes to squamous keratinizing one. This
phenomenon is called "squamous metaplasia". This lesion can be produced
also by treatment with various toxic agents, including carcinogens. The
importance of this lesion has been recognized in the development of
bronchogenic cancer. In this proposal, we propose a hypothesis of
autocrine regulation mechanism in the development of this lesion. It is
proposed that epithelial cells during vitamin A deficiency produce growth
factor and cells then use this factor for their continuous proliferation.
Normally, vitamin A controls negatively the production of this cell-derived
growth factor. In my laboratory, we have developed a serum-free,
hormone-supplemented medium for continuous proliferation of human bronchial
epithelial (HBE) cells in vitro. Properties of cultured HBE cells resemble
to those of squamous metaplastic epithelia in many aspects; such as
secretion of hyaluronate, formation of tonofilaments. Growth of cultured
HBE cells is also under the vitamin A control. In the absence of vitamin
A, cells secrete growth factor which can overcome the growth inhibition of
vitamin A under a specific condition. This phenomenon is similar to that
occurs in vivo during squamous metaplasia. Therefore, the culture system
developed in this study can be used as an in vitro model to test the
hypothesis and to elucidate the nature of this squamous phenomenon. We
propose to isolate this cell-derived growth factor and to elucidate the
chemical nature of this molecule. We would like to generate antibodies and
cDNA corresponding to this growth factor. Both of them will be used in
studies to elucidate roles of vitamin A and this growth factor in
epithelial cell growth. These studies will be able to evaluate the
potential role of "autocrine secretion" in this classic "squamous
metaplasia" of respiratory epithelium.
Effective start/end date8/1/857/31/88


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)


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