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Journal of Cell Science, Vol 98, 91-98, Copyright © 1991 by Company of Biologists

Cooperative enhancement of hyaluronic acid synthesis by combined use of IGF-I and EGF, and inhibition by tyrosine kinase inhibitor genistein, in cultured mesothelial cells from rabbit pericardial cavity

ATSUSHI HONDA 1, NAKAE NOGUCHI 1, HIROMI TAKEHARA 1, YOSHIAKI OHASHI 2, NORIKO ASUWA 3, and YO MORI 1

1 Department of Biochemistry, Tokyo College of Pharmacy, 1432-1, Horinouchi, Hachioji-shi, Tokyo 192-03, Japan
2 Department of Biochemistry, Tokyo College of Pharmacy, 1432-1, Horinouchi, Hachioji-shi, Tokyo 192-03, Japan; Present address: International Development Department, Chugai Pharmaceutical Co., Ltd, Tokyo, Japan
3 Department of Pathology, Tokyo Medical College, Shinjuku, Shinjuku-ku, Tokyo 160, Japan

Author for correspondence

We examined the combined effects of IGF-I and EGF on hyaluronic acid synthesis using cultured pericardial mesothelial cells from rabbit pericardial cavity. Combined exposure of pericardial cells to IGF-I and EGF cooperatively increased hyaluronic acid synthesis and the level of hyaluronic acid synthase activity over that seen with or without IGF-I or EGF alone, but did not significantly stimulate the sulfated glycosaminoglycan synthesis. Increase in the level of hyaluronic acid synthesis and hyaluronic acid synthase activity induced by these growth factors was blocked after pretreatment with a tyrosine-specific protein kinase inhibitor, genistein. Genistein had no direct inhibitory effect on hyaluronic acid synthase activity. These results suggest that cooperative enhancement of hyaluronic acid synthesis induced by combined use of IGF-I and EGF could be mediated by a receptor tyrosine kinase-involved transmembrane signaling process that is responsive to IGF-I and EGF.

Key words: hyaluronic acid synthesis, EGF, IGF-I, tyrosine kinase inhibitor, genistein, mesothelial cells, rabbit pericardium




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© The Company of Biologists Ltd 1991