التفاصيل البيبلوغرافية
| العنوان: |
The lysosomal cysteine protease cathepsin L regulates keratinocyte proliferation by control of growth factor recycling. |
| المؤلفون: |
Reinheckel, Thomas, Hagemann, Sascha, Dollwet-Mack, Susanne, Martinez, Elke, Lohmüller, Tobias, Zlatkovic, Gordana, Tobin, Desmond J., Maas-Szabowski, Nicole, Peters, Christoph |
| المصدر: |
Journal of Cell Science; 8/1/2005, Vol. 118 Issue 15, p3387-3395, 9p, 16 Color Photographs, 1 Diagram, 17 Graphs |
| مصطلحات موضوعية: |
KERATINOCYTES, CELL proliferation, EPIDERMAL growth factor, HYPERPLASIA, CELL membranes, GROWTH factors |
| مستخلص: |
Mice deficient for cathepsin L (CTSL) show epidermal hyperplasia due to a hyperproliferation of basal keratinocytes. Here we show that the critical function of CTSL in the skin is keratinocyte specific. This is revealed by transgenic re-expression of CTSL in the keratinocytes of ctsl-/- mice, resulting in a rescue of the ctsl-/- skin phenotype. Cultivation of primary mouse keratinocytes with fibroblast- and keratinocyte-conditioned media, as well as heterologous organotypic co-cultures of mouse fibroblasts and human keratinocytes, showed that the altered keratinocyte proliferation is caused primarily by CTSL-deficiency in keratinocytes. In the absence of EGF, wild type and CTSL-knockout keratinocytes proliferate with the same rates, while in presence of EGF, ctsl-/- keratinocytes showed enhanced proliferation compared with controls. Internalization and degradation of radioactively labeled EGF was identical in both ctsl-/- and ctsl+/+ keratinocytes. However, ctsl-/- keratinocytes recycled more EGF to the cell surface, where it is bound to the EGF-receptor, which is also more abundant in ctsl-/- cells. We conclude that the hyperproliferation of keratinocytes in CTSL-knockout mice is caused by an enhanced recycling of growth factors and growth factor receptors from the endosomes to the keratinocyte plasma membrane, which result in sustained growth stimulation. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
