Growth Factor-regulated Pathways in Epithelial Cell Proliferation

Aaronson, Stuart A.; Rubin, Jeffrey S.; Finch, Paul W.; Wong, Jane; Marchese, Cinzia; Falco, Joseph; Taylor, William G.; Kraus, Matthias H.

doi:10.1164/ajrccm/142.6_pt_2.s7

Cited by 49 publications

(25 citation statements)

References 18 publications

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“…Hepatocyte growth factor stimulates epithelial mitogenesis in several organs (29,30). Another growth factor that could be involved in mesenchymal-epithelial interactions is keratinocyte growth factor, which is secreted by mesenchymal and fibroblastic cells and stimulates epithelial cell proliferation (31). Keratinocyte growth factor is expressed in monkey uterus (32).…”

Section: Discussionmentioning

confidence: 99%

Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium

Cooke

Buchanan

Young

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

497

369

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Estradiol-17␤ (E 2 ) acts through the estrogen receptor (ER) to regulate uterine growth and functional differentiation. To determine whether E 2 elicits epithelial mitogenesis through epithelial ER versus indirectly via ERpositive stromal cells, uteri from adult ER-deficient ER knockout (ko) mice and neonatal ER-positive wild-type (wt) BALB͞c mice were used to produce the following tissue recombinants containing ER in epithelium (E) and͞or stroma (S), or lacking ER altogether: wt-S ؉ wt-E, wt-S ؉ ko-E, ko-S ؉ ko-E, and ko-S ؉ wt-E. Tissue recombinants were grown for 4 weeks as subrenal capsule grafts in intact female nude mice, then the hosts were treated with either E 2 or oil a week after ovariectomy. Epithelial labeling index and ER expression were determined by [ 3 H]thymidine autoradiography and immunohistochemistry, respectively. In tissue recombinants containing wt-S (wt-S ؉ wt-E, wt-S ؉ ko-E), E 2 induced a similar large increase in epithelial labeling index compared with oil-treated controls in both types of tissue recombinants despite the absence of epithelial ER in wt-S ؉ ko-E tissue recombinants. This proliferative effect was blocked by an ER antagonist, indicating it was mediated through ER. In contrast, in tissue recombinants prepared with ko-S (ko-S ؉ ko-E and ko-S ؉ wt-E), epithelial labeling index was low and not stimulated by E 2 despite epithelial ER expression in ko-S ؉ wt-E grafts. In conclusion, these data demonstrate that epithelial ER is neither necessary nor sufficient for E 2 -induced uterine epithelial proliferation. Instead, E 2 induction of epithelial proliferation appears to be a paracrine event mediated by ER-positive stroma. These data in the uterus and similar studies in the prostate suggest that epithelial mitogenesis in both estrogen and androgen target organs are stromally mediated events.

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Section: Discussionmentioning

confidence: 99%

Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium

Cooke

Buchanan

Young

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

497

369

View full text Add to dashboard Cite

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“…Keratinocyte growth factor (KGF/FGF-7), a member of the fibroblast growth factor (FGF) family, has been implicated as an important stroma-derived mediator of epithelial cell growth, having no mitogenic activity on cultured endothelial cells or fibroblasts (6)(7)(8)(9)(10). KGF was originally purified from the conditioned medium of a human embryonic lung fibroblast cell line (6).…”

mentioning

confidence: 99%

Pulmonary malformation in transgenic mice expressing human keratinocyte growth factor in the lung.

Simonet

Rose²,

Bucay³

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

165

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Expression of human keratinocyte growth factor (KGF/FGF-7) was directed to epithelial cells of the developing embryonic lung of transgenic mice disrupting normal pulmonary morphogenesis during the pseudoglandular stage of development. By embryonic day 15.5 (E15.5), lungs of transgenic surfactant protein C (SP-C)-KGF mice resembled those of humans with pulmonary cystadenoma. Lungs were cystic, filling the thoracic cavity, and were composed of numerous dilated saccules lined with glycogen-containing columnar epithelial cells. The normal distribution of SP-C proprotein in the distal regions of respiratory tubules was disrupted. Columnar epithelial cells lining the papillary structures stained variably and weakly for this distal respiratory cell marker. Mesenchymal components were preserved in the transgenic mouse lungs, yet the architectural relationship of the epithelium to the mesenchyme was altered. SP-C-KGF transgenic mice failed to survive gestation to term, dying before E17.5. Culturing mouse fetal lung explants in the presence of recombinant human KGF also disrupted branching morphogenesis and resulted in similar cystic malformation of the lung. Thus, it appears that precise temporal and spatial expression of KGF is likely to play a crucial role in the control of branching morphogenesis during fetal lung development.

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“…Some oncogenes, which represent constitutively activated forms of genes critically involved in growthfactor signalling pathways, bypass the requirement for mitogens of the EGF pathway (Aaronson et al 1990). …”

Section: Figurementioning

confidence: 99%

Keratinocyte Growth Factor and Epidermal Growth Factor Can Reverse the Intestinal Atrophy Associated with Elemental Diets in Mice

Sasaki

Fitzgerald

Mandir

et al. 2003

Experimental Physiology

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Elemental diets are associated with intestinal atrophy and reduced intestinal integrity. Growth factors such as keratinocyte growth factor (KGF) and epidermal growth factor (EGF) have considerable potential for the therapeutic reversal of such atrophy and may have greater actions if given in combination. We examined the effects of recombinant human KGF (rHuKGF), EGF and their combination on tissue mass, cell proliferation and crypt fission throughout the intestine of mice fed elemental diets. rHuKGF significantly increased the relative wet weight of the intestine, with EGF having a lesser effect. Cell proliferation of the stomach, small intestine and colon were significantly increased by rHuKGF, but EGF only increased proliferation in the small intestine. Crypt fission in the small intestine and colon was significantly decreased by rHuKGF. An interactive effect of rHuKGF and EGF on the weight of stomach and the proliferation of the fundus and antrum was observed. Moreover, an interactive effect of the agents was also seen on crypt fission in the colon. We concluded that (1) rHuKGF and EGF have significant trophic effects on the stomach, small intestine and colon, (2) these actions vary between different sites in the gastrointestinal tract, and (3) interactive effects occur. Experimental Physiology (2003) 88.2, 261-267. 2466 Publication of The Physiological Society

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Growth Factor-regulated Pathways in Epithelial Cell Proliferation

Cited by 49 publications

References 18 publications

Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium

Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium

Pulmonary malformation in transgenic mice expressing human keratinocyte growth factor in the lung.

Keratinocyte Growth Factor and Epidermal Growth Factor Can Reverse the Intestinal Atrophy Associated with Elemental Diets in Mice

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