PMID:23372771

Citation	Jean, JC, George, E, Kaestner, KH, Brown, LA, Spira, A and Joyce-Brady, M (2013) Transcription factor klf4, induced in the lung by oxygen at birth, regulates perinatal fibroblast and myofibroblast differentiation. PLoS ONE 8:e54806
Abstract	The fluid-filled lung exists in relative hypoxia in utero (∼25 mm Hg), but at birth fills with ambient air where the partial pressure of oxygen is ∼150 mm Hg. The impact of this change was studied in mouse lung with microarrays to analyze gene expression one day before, and 2, 6, 12 and 24 hours after birth into room air or 10% O(2). The expression levels of >150 genes, representing transcriptional regulation, structure, apoptosis and antioxidants were altered 2 hrs after birth in room air but blunted or absent with birth in 10% O(2). Kruppel-like factor 4 (Klf4), a regulator of cell growth arrest and differentiation, was the most significantly altered lung gene at birth. Its protein product was expressed in fibroblasts and airway epithelial cells. Klf4 mRNA was induced in lung fibroblasts exposed to hyperoxia and constitutive expression of Klf4 mRNA in Klf4-null fibroblasts induced mRNAs for p21(cip1/Waf1), smooth muscle actin, type 1 collagen, fibronectin and tenascin C. In Klf4 perinatal null lung, p21(cip1/Waf1)mRNA expression was deficient prior to birth and associated with ongoing cell proliferation after birth; connective tissue gene expression was deficient around birth and smooth muscle actin protein expression was absent from myofibroblasts at tips of developing alveoli; p53, p21(cip1/Waf1) and caspase-3 protein expression were widespread at birth suggesting excess apoptosis compared to normal lung. We propose that the changing oxygen environment at birth acts as a physiologic signal to induce lung Klf4 mRNA expression, which then regulates proliferation and apoptosis in fibroblasts and airway epithelial cells, and connective tissue gene expression and myofibroblast differentiation at the tips of developing alveoli.
Links	PubMed PMC3553006 Online version:10.1371/journal.pone.0054806
Keywords
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:KLF4	involved_in	GO:0006351: transcription, DNA-templated	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:KLF4		GO:0006351: transcription, DNA-dependent	ECO:0000315:		P		As Figure 7A and 7B display, KLF4 is involved in regulation of cell differentiation.	complete CACAO 6408

References

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