Keratinocyte growth factor and hepatocyte growth factor/scatter factor are heparin-binding growth factors for alveolor type II cells in fibroblast-conditioned medium

Proliferation of type II cells is required for maintenance of the alveolar epithelium and for restoration after lung injury. Although various known growth factors have been reported to stimulate type II cell proliferation in vitro, there is very little knowledge on which growth factors are present in the lung in vivo. We have previously reported that rat lavage fluid contains a mitogen(s) for type II cells, and this study was de signed to identify the growth factor(s) in this biological fluid for type II cells. The mitogenic activity was purified by sequential chromatography on blue Sepharose and heparin Sepharose. Hepatocyte growth factor (HGF) and acidic fibroblast growth factor by Western analysis. The amount of HGF recovered by lavage was approximately 6 ng/rat. By a use of neutralizing antibodies for different growth factors, HGF was found to be responsible for most of the stimulatory activity for rat type II cells in the partially purified lavage fluid. In addition to HGF, rat lavage fluid also contained potent mitogenic activity for fibroblasts. Finally, we have demonstrated that much of the mitogenic activity in salt extracts of human lung is HGF. We conclude that HGF is found in rat lavage fluid and is possibly an important mitogen for adult type II cells in vivo.

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Keratinocyte growth factor increases mRNAs for SP-A and SP-B in adult rat alveolar type II cells in culture

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1995.269.3.l344 ◽

1995 ◽

Vol 269 (3) ◽

pp. L344-L350 ◽

Cited By ~ 23

Author(s):

K. Sugahara ◽

J. S. Rubin ◽

R. J. Mason ◽

E. L. Aronsen ◽

J. M. Shannon

Keyword(s):

Growth Factors ◽

Growth Factor ◽

Keratinocyte Growth Factor ◽

Primary Cultures ◽

Surfactant Proteins ◽

Alveolar Type ◽

Type Ii Cells ◽

Type Ii ◽

Alveolar Type Ii Cells ◽

Adult Rat

The production of pulmonary surfactant, a complex of phospholipids and lung-specific surfactant proteins, is a primary function of alveolar type II cells. Although 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 two- to threefold increase in steady-state levels of mRNAs for SP-A and SP-B, but had no effect on 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 they could be neutralized by a monoclonal antibody against KGF. The effects of KGF were mimicked by acidic fibroblast growth factor, 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, thus suggesting an important role for KGF in maintenance of the alveolar epithelium.

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Effect of hepatocyte growth factor in amniotic fluid on fetal alveolar type II cells

Placenta ◽

10.1016/0143-4004(95)90044-6 ◽

1995 ◽

Vol 16 (7) ◽

pp. A4

Author(s):

Atsuo Itakura ◽

Osamu Kurauchi ◽

Tomomitsi Okamoto ◽

Shigehiko Morikawa ◽

Kazunori Furugori ◽

...

Keyword(s):

Growth Factor ◽

Hepatocyte Growth Factor ◽

Amniotic Fluid ◽

Alveolar Type ◽

Type Ii Cells ◽

Type Ii ◽

Alveolar Type Ii Cells ◽

Hepatocyte Growth

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Autocrine Interactions of Keratinocyte Growth Factor, Hepatocyte Growth Factor, and Kit-Ligand in the Regulation of Normal Ovarian Surface Epithelial Cells*

Endocrinology ◽

10.1210/endo.141.7.7581 ◽

2000 ◽

Vol 141 (7) ◽

pp. 2532-2539 ◽

Cited By ~ 22

Author(s):

Jeff A. Parrott ◽

Rachel Mosher ◽

Grace Kim ◽

Michael K. Skinner

Keyword(s):

Ovarian Cancer ◽

Growth Factors ◽

Growth Factor ◽

Hepatocyte Growth Factor ◽

Keratinocyte Growth Factor ◽

Ovarian Surface Epithelium ◽

Surface Epithelium ◽

Kit Ligand ◽

Ovarian Surface ◽

Hepatocyte Growth

Ovarian tumors are primarily derived from the layer of epithelium surrounding the ovary termed the ovarian surface epithelium (OSE). Although extensive research has focused on established ovarian tumors, relatively little is known about the normal biology of the OSE that gives rise to ovarian cancer. The local expression and actions of growth factors are likely involved in both normal and tumorigenic OSE biology. The current study investigates the expression and action of keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), and kit-ligand (KL) in normal ovarian surface epithelium (OSE). The actions of various growth factors on KGF, HGF, and KL expression are examined. Observations indicate that freshly isolated normal OSE express the genes for KGF, HGF, and KL and expression is maintained in vitro. KGF messenger RNA expression in OSE was found to be stimulated by KGF and HGF, but not KL. HGF expression in OSE was found to be stimulated by KGF, HGF, and KL. KL expression in OSE was also found to be stimulated by KGF, HGF, and KL. Therefore, the various growth factors can regulate the mRNA expression of each other in OSE. Effects of growth factors on OSE growth were examined. KGF, HGF, and KL stimulated OSE growth to similar levels as the positive control epidermal growth factor. Observations suggest that KGF, HGF, and KL interact to promote OSE growth and growth factor expression. The ability of these growth factors to interact in a positive autocrine feedback loop is postulated to be important for normal OSE biology. Paracrine interactions with the adjacent stromal cells will also be a factor in OSE biology. Abnormal interactions of these growth factors may be involved in the onset and progression of ovarian cancer.

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