Met-/- kidneys express epithelial cells which chemotax and form
tubules in response to egf receptor ligands.
Kjelsberg, Crystal, Hiroyuki Sakurai, Katherine Spokes, Carmen
Birchmeier, Iain Drummond, Sanjay Nigam, and Lloyd G. Cantley.
Division of Nephrology, Beth Israel Hospital, Harvard Medical
School, Renal Division, Brigham and Women's Hospital, Harvard Medical
School, Boston, MA 02215, Division of Nephrology, Massachusetts
General Hospital, Boston, MA, and Max-Delbr[umlaut]uck-Centrum
F[umlaut]ur Molekulare Medizin, Berlin, Germany
APStracts 3:0198F, 1996.
The growth factor/receptor combination of hepatocyte growth factor
(HGF)/c-met has been postulated to be critical for mesenchymal to
epithelial conversion and tubule formation in the developing kidney.
We therefore isolated and immortalized cells from embryonic kidneys
of met-/- transgenic mice to determine if these cells were epithelial
and able to chemotax and form tubules in vitro. The cells were
immortalized with retrovirus expressing HPV 16 E6/E7 genes. Two
rapidly dividing clones were isolated and found to express the
epithelial cell markers cytokeratin, ZO-1, and E-cadherin, but not to
express the fibroblast marker vimentin. The met-/- cells were able to
chemotax in response to EGF and TGF[alpha] and form tubules in vitro
in response to TGFa, but not HGF. These experiments suggest that the
HGF/c-met axis is not essential for epithelial cell development in
the embryonic kidney and demonstrate that other growth factors are
capable of supporting early tubulogenesis.
Received 30 August 1996; accepted in final form 22 October 1996.
APS Manuscript Number F254-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996