Keratinocyte growth factor (kgf) increases mrnas for sp-a and sp-b
in adult rat alveolar type ii cells in primary culture.
Sugahara, Kazuhiro, Jeffrey S. Rubin, Robert J. Mason*, Elizabeth L.
Aronsen, and John M. Shannon.
Department of Medicine, National Jewish Center for Immunology and
Respiratory Medicine, Denver, CO and Laboratory of Cellular and
Molecular Biology, National Cancer Institute, Bethesda, MD
APStracts 2:0081L, 1995.
The production of pulmonary surfactant, a complex of phospholipids and
lung-specific surfactant proteins is a primary function of alveolar
type II cells. While previous studies have demonstrated a role for
cell-extracellular matrix interactions and normal cell shape in the
maintenance of differentiated function in primary cultures of adult
rat type II cells, a positive role for growth factors in surfactant
protein gene expression in isolated normal adult type II cells has
not been reported. In the present study we have examined the effects
of a panel of hormones, growth factors and cytokines on the
expression of mRNAs for surfactant proteins A, B, and C (SP-A, SP-B,
and SP-C). Our results show that keratinocyte growth factor (KGF)
induced a 2-3 fold increase in steady-state levels of mRNAs for SP-A
and SP-B, but had no effect, or decreased, SP-C mRNA. The increase in
SP-A mRNA was accompanied by an increase in SP-A protein. The effects
of KGF were both dose- and time-dependent, and could be neutralized
by a monoclonal antibody against KGF. The effects of KGF were
mimicked by acidic FGF, which will bind the KGF receptor. We conclude
that KGF can support differentiation of alveolar type II cells as
well as act as a mitogen, and thus suggest an important role for KGF
in maintenance of the alveolar epithelium.
Received 24 February 1995; accepted in final form 25 April 1995.
APS Manuscript Number L57-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 16 May 1995.