Kruppel-like factor 5 is required for perinatal lung morphogenesis and function

Abstract

The transition to air breathing after birth requires both anatomic and biochemical maturation of the lung. Lung morphogenesis is mediated by complex paracrine interactions between respiratory epithelial cells and mesenchymal cells that direct transcriptional programs guiding patterning and cytodifferentiation of the lung. In the present study, transgenic mice were generated in which the Kruppel-like factor 5 gene (Klf5) was conditionally deleted in respiratory epithelial cells in the fetal lung. Lack of KLF5 inhibited maturation of the lung during the saccular stage of development. Klf5Δ/Δ mice died of respiratory distress immediately after birth. Abnormalities in lung maturation and morphogenesis were observed in the respiratory epithelium, the bronchiolar smooth muscle, and the pulmonary vasculature. Respiratory epithelial cells of both the conducting and peripheral airways were immature. Surfactant phospholipids were decreased and lamellar bodies, the storage form of surfactant, were rarely found. mRNA microarray analysis demonstrated that KLF5 influenced the expression of genes regulating surfactant lipid and protein homeostasis, vasculogenesis, including Vegfa, and smooth muscle cell differentiation. KLF5 regulates genes controlling paracrine interactions during lung morphogenesis, as well as those regulating the maturation of the respiratory epithelium that is required for lung function after birth.

Krüppel-like factor 5 promotes breast cell proliferation partially through upregulating the transcription of fibroblast growth factor binding protein 1

“…In contrast, the upregulation of FGF-BP by KLF5 appears not to be limited in breast cancer. In the TSU-Pr1 bladder cancer cell line (Figures 2b and 6b) and the mouse lung (Chen et al, 2006;Wan et al, 2008), FGF-BP is also positively regulated by KLF5. Several lines of evidence presented in Figure 6 strongly suggest that KLF5 promotes DNA synthesis partially through FGF-BP.…”

“…First, both KLF5 and FGF-BP were reported to be induced by TPA (Harris et al, 1998;Sun et al, 2001;Sur et al, 2002) and the MAPK pathway (Harris et al, 2001;Sun et al, 2001;Chanchevalap et al, 2006). In addition, microarray studies suggest that FGF-BP is a downstream gene of KLF5 in vitro and in vivo (Chen et al, 2006;Wan et al, 2008). Functionally, both genes promote cell transformation and angiogenesis (Czubayko et al, 1997;Shindo et al, 2002).…”

“…FGF-BP was identified as one of the KLF5 downstream target genes by two independent microarray studies (Chen et al, 2006;Wan et al, 2008), we thus wondered if both KLF5 and FGF-BP proteins are co-expressed in breast cancer. Indeed, we found that both proteins are co-expressed in four ER-negative breast cell lines (MCF10A, SW527, BT20 and HCC1937) by immunoblotting ( Figure 1a).…”

“…KLF5 has been shown to regulate transcription of a number of genes, such as the platelet-derived growth factor-a (PDGF-a) (Aizawa et al, 2004), CyclinD1 (Bateman et al, 2004), Pim1 (Zhao et al, 2008) and PPARg in different cell models. Two microarray studies revealed many KLF5-regulated genes in vitro and in vivo (Chen et al, 2006;Wan et al, 2008). Among these KLF5-regulated genes, the fibroblast growth factor binding protein 1 (FGF-BP/HBP17) has been repeatedly identified (Chen et al, 2006;Wan et al, 2008).…”

“…Two microarray studies revealed many KLF5-regulated genes in vitro and in vivo (Chen et al, 2006;Wan et al, 2008). Among these KLF5-regulated genes, the fibroblast growth factor binding protein 1 (FGF-BP/HBP17) has been repeatedly identified (Chen et al, 2006;Wan et al, 2008).…”