Keratinocyte growth factor and its receptor are involved in regulating early lung branching - PubMed (original) (raw)
Keratinocyte growth factor and its receptor are involved in regulating early lung branching
M Post et al. Development. 1996 Oct.
Abstract
Lung branching morphogenesis depends on mesenchymal-epithelial tissue interactions. Keratinocyte growth factor (KGF) has been implicated to be a regulator of these tissue interactions. In the present study, we investigated the role of KGF in early rat lung organogenesis. Reverse transcriptase-polymerase chain reaction analysis revealed KGF mRNA expression in the mesenchymal component of the 13-day embryonic lung, while message for KGF receptor (KGFR) was expressed in the epithelium, confirming the paracrine nature of KGF/KGFR axis. Antisense KGF oligonucleotides inhibited DNA synthesis of embryonic lung explants. This inhibitory effect of antisense KGF was partially reversed by the addition of exogenous KGF. Recombinant KGF was mitogenic for 13-day isolated embryonic lung epithelial cells. Medium conditioned by 13-day lung mesenchymal cells also stimulated DNA synthesis of 13-day embryonic lung epithelial cells. This stimulatory effect was partially abrogated by a neutralizing KGF antibody. The number of terminal buds of lung explants cultured in the presence of antisense KGF oligonucleotides was significantly reduced compared to control explants. Exogenous KGF partially abrogated the inhibitory effect of antisense KGF on early lung branching. Sense or scrambled KGF oligonucleotides had no inhibitory effect on lung growth and branching. Addition of neutralizing KGF antibodies to the explants also reduced the degree of branching, while non-immune IgG and neutralizing acidic FGF antibodies had no effect. Explants incubated with antisense oligonucleotides targeted to the initiation site of translation of both the splice variants of the fibroblast growth factor receptor-2 (FGFR2) gene, KGFR and bek, exhibited a similar reduction in lung branching as observed with antisense KGF oligonucleotides. Antisense KGFR-specific oligonucleotides dramatically inhibited lung branching, while exposure of explants to antisense bek-specific oligonucleotides resulted in reduced branching albeit to a lesser degree than that observed with antisense KGFR-specific oligonucleotides. Neither sense nor scrambled KGFR-specific oligonucleotides had any effect on early lung branching. These results suggest that the KGF/KGFR system has a critical role in early lung organogenesis.
Similar articles
- Keratinocyte growth factor and embryonic rat lung morphogenesis.
Shiratori M, Oshika E, Ung LP, Singh G, Shinozuka H, Warburton D, Michalopoulos G, Katyal SL. Shiratori M, et al. Am J Respir Cell Mol Biol. 1996 Sep;15(3):328-38. doi: 10.1165/ajrcmb.15.3.8810636. Am J Respir Cell Mol Biol. 1996. PMID: 8810636 - Differential effect of cell-associated heparan sulfates on the binding of keratinocyte growth factor (KGF) and acidic fibroblast growth factor to the KGF receptor.
Reich-Slotky R, Bonneh-Barkay D, Shaoul E, Bluma B, Svahn CM, Ron D. Reich-Slotky R, et al. J Biol Chem. 1994 Dec 23;269(51):32279-85. J Biol Chem. 1994. PMID: 7528211 - Keratinocyte growth factor as a cytokine that mediates mesenchymal-epithelial interaction.
Rubin JS, Bottaro DP, Chedid M, Miki T, Ron D, Cunha GR, Finch PW. Rubin JS, et al. EXS. 1995;74:191-214. doi: 10.1007/978-3-0348-9070-0_10. EXS. 1995. PMID: 8527895 Review. - Keratinocyte growth factor.
Rubin JS, Bottaro DP, Chedid M, Miki T, Ron D, Cheon G, Taylor WG, Fortney E, Sakata H, Finch PW, et al. Rubin JS, et al. Cell Biol Int. 1995 May;19(5):399-411. doi: 10.1006/cbir.1995.1085. Cell Biol Int. 1995. PMID: 7640656 Review.
Cited by
- Cloning and expression analysis of Fgf5, 6 and 7 during early chick development.
Kumar M, Chapman SC. Kumar M, et al. Gene Expr Patterns. 2012 Aug-Sep;12(7-8):245-53. doi: 10.1016/j.gep.2012.05.002. Epub 2012 May 24. Gene Expr Patterns. 2012. PMID: 22634565 Free PMC article. - Hyperoxia-induced NF-kappaB activation occurs via a maturationally sensitive atypical pathway.
Wright CJ, Zhuang T, La P, Yang G, Dennery PA. Wright CJ, et al. Am J Physiol Lung Cell Mol Physiol. 2009 Mar;296(3):L296-306. doi: 10.1152/ajplung.90499.2008. Epub 2008 Dec 12. Am J Physiol Lung Cell Mol Physiol. 2009. PMID: 19074556 Free PMC article. - Efficient generation of lung and airway epithelial cells from human pluripotent stem cells.
Huang SX, Islam MN, O'Neill J, Hu Z, Yang YG, Chen YW, Mumau M, Green MD, Vunjak-Novakovic G, Bhattacharya J, Snoeck HW. Huang SX, et al. Nat Biotechnol. 2014 Jan;32(1):84-91. doi: 10.1038/nbt.2754. Epub 2013 Dec 1. Nat Biotechnol. 2014. PMID: 24291815 Free PMC article. - Lung organogenesis.
Warburton D, El-Hashash A, Carraro G, Tiozzo C, Sala F, Rogers O, De Langhe S, Kemp PJ, Riccardi D, Torday J, Bellusci S, Shi W, Lubkin SR, Jesudason E. Warburton D, et al. Curr Top Dev Biol. 2010;90:73-158. doi: 10.1016/S0070-2153(10)90003-3. Curr Top Dev Biol. 2010. PMID: 20691848 Free PMC article. Review.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous