Keratinocyte growth factor is a growth factor for type II pneumocytes in vivo.

Ulich, Thomas R.; Yi, Eunhee S.; Longmuir, Kenneth J.; Su, Yin; Biltz, Rebecca; Morris, Charles F.; Housley, Regina M.; Pierce, Glenn F.

doi:10.1172/jci117086

Cited by 337 publications

(266 citation statements)

References 14 publications

(4 reference statements)

Supporting

Mentioning

239

Contrasting

Unclassified

Order By: Relevance

“…In the present experiments, the same recombinant VEGF at the same concentrations failed to induce any increase in thymidine or BrdU incorporation in isolated type II cells, which, by contrast, responded strongly to KGF, consistent with previous findings in adult (26,35) as well as fetal (7) type II cells. Our findings, therefore, suggest that the proliferative effects of VEGF previously observed in lung explants were indirect.…”

Section: Discussionsupporting

confidence: 93%

Effects of vascular endothelial growth factor on isolated fetal alveolar type II cells

Raoul¹,

Chailley‐Heu²,

Barlier-Mur³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Previous investigations gained from in vivo or lung explant studies suggested that VEGF is an autocrine proliferation and maturation factor for developing alveolar type II cells. The objective of this work was to determine whether VEGF exerted its growth and maturation effects directly on isolated type II cells. These were isolated from 19-day fetal rat lung and cultured in defined medium. The presence of VEGF receptor-2 was assessed in cultured cells at the pre- and posttranslational levels. Recombinant VEGF165, formerly found to be active on lung explants, failed to enhance type II cell proliferation estimated by thymidine and 5-bromo-2′-deoxy-uridine incorporation. It increased choline incorporation in saturated phosphatidylcholine by 27% but did not increase phospholipid surfactant pool size. VEGF (100 ng/ml) left unchanged the transcript level of surfactant proteins (SP)-A, SP-C, and SP-D but increased SP-B transcripts to four times the control steady-state level. VEGF slightly retarded, but did not prevent, the in vitro transdifferentiation of type II into type I cells, as assessed by immunolabeling of the type I cell marker T1α. We conclude that, with the exception of SP-B expression, which appears to be controlled directly, the previously observed effects of this VEGF isoform on type II cells are likely to be exerted indirectly through reciprocal paracrine interactions involving other lung cell types.

show abstract

Section: Discussionsupporting

confidence: 93%

Effects of vascular endothelial growth factor on isolated fetal alveolar type II cells

Raoul¹,

Chailley‐Heu²,

Barlier-Mur³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…However, other experimental approaches will be required to fully define the precise nature of KGF involvement in epithelial development. In this regard, earlier cell and organ culture studies have demonstrated that KGF is a paracrine mitogen for epithelial cells from a variety of different sources (Aaronson et al, 1991;Marchese et al, 1990;Pierce et al, 1994;Rubin et al, 1989;Ulich et al, 1994), as well as a morphogen in the ductal branching morphogenesis of the neonatal mouse seminal vesicle (Alarid et al, 1994) and the neonatal rat prostate (Sugimura et al, 1993). The extension of similar studies to other organ systems will provide a powerful approach in further elucidating the multiple roles of KGF during development.…”

Section: Discussionmentioning

confidence: 99%

Pattern of keratinocyte growth factor and keratinocyte growth factor receptor expression during mouse fetal development suggests a role in mediating morphogenetic mesenchymal‐epithelial interactions

Finch

Cunha

Rubin

et al. 1995

Developmental Dynamics

266

172

View full text Add to dashboard Cite

Mesenchymal cells are required for the induction of epithelial development during mammalian organogenesis. Keratinocyte growth factor (KGF) is a mesenchymally derived mitogen with specific activity for epithelial cells, suggesting that it may play a role in mediating these interactions. To further evaluate this hypothesis, in situ hybridization was used to examine the spatial distribution of KGF and KGF receptor (KGFR) transcripts during organogenesis and limb formation in mouse embryos (days 14.5 through 16.5). To facilitate this aim, mouse KGF cDNA clones were isolated. There was extensive identity between the deduced mouse KGF protein sequence and that of its human and rat cognates, indicating that this gene has been highly conserved during mammalian evolution. In addition, mouse KGF protein was purified from fibroblasts and demonstrated to be structurally and functionally similar to human KGF protein. For organs within the integumental, respiratory, gastrointestinal, and urogenital systems, whose development is dependent upon mesenchymal‐epithelial interactions, KGF mRNA was detected in mesenchymal cells, while epithelial cells expressed transcripts for the KGFR. KGF and KGFR mRNA was also expressed in certain other tissues such as perichondrium, cartilage of developing bones, developing skeletal muscle, and visceral smooth muscle whose development is not regulated by mesenchymal‐epithelial interactions. KGF expression was also detected in tissues isolated from human embryos, suggesting similar functions for KGF in human development. Taken together, our results suggest that KGF plays an important role in mediating mesenchymal‐epithelial interactions during organogenesis, but may also have other developmental functions in tissues not governed by such interactions. ©1995 Wiley‐Liss, Inc.

show abstract

“…In the alveolar epithelium, this progenitor cell-like function has been ascribed to AEC2 (13,31,36). AEC2 proliferate during embryonic and fetal life but, in the adult lung, in the absence of injury, are highly differentiated and do not normally divide (9,37). However, in response to environmental insult, some AEC2 become both hypertrophic and hyperplastic, such that cells undergo phenotypic and functional changes (17,24).…”

mentioning

confidence: 99%

Contribution of proliferation and DNA damage repair to alveolar epithelial type 2 cell recovery from hyperoxia

Lee

Reddy²,

Barsky³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

. Contribution of proliferation and DNA damage repair to alveolar epithelial type 2 cell recovery from hyperoxia. Am J Physiol Lung Cell Mol Physiol 290: L685-L694, 2006. First published November 18, 2005 doi:10.1152/ajplung.00020.2005In this study, C57BL/6J mice were exposed to hyperoxia and allowed to recover in room air. The sublethal dose of hyperoxia for C57BL/6J was 48 h. Distal lung cellular isolates from treated animals were characterized as 98% epithelial, with minor fibroblast and endothelial cell contaminants. Cells were then verified as 95% pure alveolar epithelial type II cells (AEC2) by surfactant protein C (SP-C) expression. After hyperoxia exposure in vivo, fresh, uncultured AEC2 were analyzed for proliferation by cell yield, cell cycle, PCNA expression, and telomerase activity. DNA damage was assessed by TdT-dUTP nick-end labeling, whereas induction of DNA repair was evaluated by GADD-153 expression. A baseline level for proliferation and damage was observed in cells from control animals that did not alter significantly during acute hyperoxia exposure. However, a rise in these markers was observed 24 h into recovery. Over 72 h of recovery, markers for proliferation remained elevated, whereas those for DNA damage and repair peaked at 48 h and then returned back to baseline. The expression of GADD-153 followed a distinct course, rising significantly during acute exposure and peaking at 48 h recovery. These data demonstrate that in healthy, adult male C57BL/6J mice, AEC2 proliferation, damage, and repair follow separate courses during hyperoxia recovery and that both proliferation and efficient repair may be required to ensure AEC2 survival. C57BL/6J; GADD-153; telomerase IN LATE GESTATION OF MICE and rats, the alveolar epithelial cell (AEC) lineage develops from a multipotent population of stem cells that line the primitive respiratory tract (15). Alveolar epithelial type 2 cells (AEC2) manufacture surfactant and can differentiate, as required, into alveolar epithelial type 1 cells (AEC1), which regulate the gas exchange function of the organ (2, 14). To replace damaged cells throughout the life span of any animal, a particular subpopulation within the total population must retain the ability to divide. In the alveolar epithelium, this progenitor cell-like function has been ascribed to AEC2 (13,31,36). AEC2 proliferate during embryonic and fetal life but, in the adult lung, in the absence of injury, are highly differentiated and do not normally divide (9, 37). However, in response to environmental insult, some AEC2 become both hypertrophic and hyperplastic, such that cells undergo phenotypic and functional changes (17, 24). Regenerating rat AEC2 exhibit elevated cyclin and cyclin-dependent kinase (cdk) expression and activity during recovery following injury, indicating the regain of proliferative function (10, 39). During this period, the number of proliferating AEC2 has been reported to increase severalfold in rats (10, 36), mice (2), and humans (4). In human patients, this phase of recovery fr...

show abstract

Keratinocyte growth factor is a growth factor for type II pneumocytes in vivo.

Abstract: Clin. Invest. 1994.93:1298-1306

Cited by 337 publications

References 14 publications

Effects of vascular endothelial growth factor on isolated fetal alveolar type II cells

Effects of vascular endothelial growth factor on isolated fetal alveolar type II cells

Pattern of keratinocyte growth factor and keratinocyte growth factor receptor expression during mouse fetal development suggests a role in mediating morphogenetic mesenchymal‐epithelial interactions

Contribution of proliferation and DNA damage repair to alveolar epithelial type 2 cell recovery from hyperoxia

Contact Info

Product

Resources

About