Disease relevance of Fgf7

• In the present study, we attempted to immunohistochemically determine the localization of FGF-7 and FGF-10 in pancreatic tissues of an L-arginine-induced rat pancreatitis model [1].
• Administration of KGF also protects the lung from a variety of injuries and subsequent development of fibrosis [2].
• Because transforming growth factor (TGF)-beta has been shown to inhibit epithelial cell proliferation and surfactant protein gene expression in other systems and is thought to be a major effector in pulmonary fibrosis, we sought to determine if TGF-beta would antagonize the effects of KGF in primary cultures of alveolar type II cells [2].
• Pretreatment with keratinocyte growth factor (KGF) ameliorates experimentally induced acute lung injury in rats [3].
• The purpose of this study is to evaluate the role of keratinocyte growth factor (KGF), transforming growth factor-alpha (TGF-alpha), and their receptors in altered renal growth caused by complete ureteral obstruction in the developing kidney [4].

High impact information on Fgf7

• In addition, KGF increased the mRNA levels of the transcription factors CCAAT/enhancer-binding protein alpha (C/EBPalpha) and C/EBPdelta as well as SREBP-1c (ADD-1), but not PPARgamma [5].
• We developed culture conditions in which keratinocyte growth factor (KGF) stimulates fatty acid and phospholipid synthesis [5].
• In summary, KGF stimulates lipogenesis in type II cells by a coordinated expression of lipogenic enzymes and transport proteins regulated by C/EBP isoforms and SREBP-1c [5].
• KGF stimulated acetate incorporation into phosphatidylcholine, disaturated phosphatidylcholine, and phosphatidylglycerol more than 5% rat serum alone [5].
• 6 h after administration, immunoreactive KGF was observed within the lung parenchyma and along alveolar epithelial cell membranes [6].

Chemical compound and disease context of Fgf7

• Keratinocyte growth factor (KGF), a potent growth factor for type II pneumocytes and Clara cells, has been shown to prevent the end-stage pulmonary fibrosis and mortality in a rat model of bleomycin-induced lung injury [7].
• METHODS: KGF was administered before or after induction of colitis with 2,4,6-trinitrobenzenesulfonic acid/ethanol [8].
• To determine whether keratinocyte growth factor (KGF), an epithelial and urothelial growth factor, ameliorates cyclophosphamide (CP)-induced cystitis in rats, KGF (5 mg/kg) was injected in rats as a single i.v. injection 24 h prior to i.p. injection of CP (200 mg/kg) [9].
• Keratinocyte growth factor (KGF) is a heparin-binding growth factor that causes alveolar type II pneumocyte hyperplasia [10].
• Keratinocyte growth factor (KGF) prevents alpha-naphthylthiourea (ANTU)-induced permeability edema ex vivo [11].

Biological context of Fgf7

• Keratinocyte growth factor (KGF) activates keratinocyte migration and stimulates wound healing [12].
• Hyaluronan, an extracellular matrix glycosaminoglycan that accumulates in wounded epidermis, is known to promote cell migration, suggesting that increased synthesis of hyaluronan might be associated with the KGF response in keratinocytes [12].
• KGF mRNA was low before smooth muscle differentiation at 14 days' gestation, then increased [13].
• KGF gene expression was very weak or absent in 1, 3, and 6 month old rat dorsal and ventral lobes of prostate whereas it re-expressed in 9, 12, 18, 24 and 30 month old rat prostate [14].
• These data indicate that FGF7 is necessary, but not sufficient by itself, to induce the distal rat lung epithelial phenotype, and that FGF7 and FGF10 play distinct roles in lung development [15].

Anatomical context of Fgf7

• We hypothesized that KGF may protect the lung not only by inducing proliferation but also by promoting epithelial repair via enhanced epithelial cell migration [16].
• KGF reduced cytoskeleton stiffness as measured by magnetic twisting cytometry and increased cell motility (5.8 +/- 0.42 microm/h with KGF vs 3.7 +/- 0.41 microm/h in controls) [16].
• KGF acted primarily by inducing lamellipodia emission (73.2 +/- 3.9% of KGF-treated cells had lamellipodia vs 61.3 +/- 3.4% of control cells) and increasing their relative surface area (59 +/- 2.7% with KGF vs 48 +/- 2.0% in controls) [16].
• To further delineate KGF properties as a mesenchymal mediator, we wondered about its possibility to relay glucocorticoid-stimulating activity on the synthesis of the phospholipid moiety of surfactant in fetal lung fibroblasts [17].
• Here, we investigated, among the factors produced by lung mesenchyme, the part attributable to KGF in the control of surfactant synthesis [17].

Associations of Fgf7 with chemical compounds

• Moreover, anti-KGF antibody totally abolished the further increase of FCM-stimulating activity induced by dexamethasone [17].
• Using a KGF-neutralizing antibody, we assessed surfactant phospholipid synthesis by measuring choline incorporation into disaturated phosphatidylcholine of isolated fetal type II cells [17].
• FGF-10 requires 1.4 times higher NaCl for elution from immobilized heparin than does FGF-7 and binds to four times the number of sites on the pericellular matrix of epithelial cells [18].
• Analysis of mRNA expression by RNase protection revealed that, similar to FGF-7, the expression of FGF-10 was responsive to androgen in stromal cells from normal prostate and non-malignant differentiated tumors [18].
• Overexpression of a dominant-negative form of SREBP-1 decreased lipogenesis and decreased the induction of fatty acid synthase and stearyl coenzyme A desaturase-1 by KGF [19].

Regulatory relationships of Fgf7

• Glypican-1 differed from heparin in that it stimulated FGF-1 but not FGF-7 activities in BaF/KGFR cells [20].

Other interactions of Fgf7

• The data indicate that Has2 and Has3 belong to the targets of KGF in keratinocytes, and support the idea that enhanced hyaluronan synthesis acts an effector for the migratory response of keratinocytes in wound healing, whereas it may delay keratinocyte terminal differentiation [12].
• The mRNA of receptors for KGF and EGF remained essentially unchanged throughout bladder development [13].
• In support of this notion, UBs cultured in the presence of fibroblast growth factor 7 (FGF7), which induces the formation of globular structures with little distinction between the stalk and ampullae [Mech. Dev. 109 (2001) 123], and TGF-beta superfamily members lead to the formation of UBs with clear stalks and ampullae [21].
• In the pancreatic tissues of rats with L-arginine-induced pancreatitis, FGF-7 was localized in alpha cells, whereas FGF-10 was expressed in vascular smooth muscle cells (VSMCs) [1].
• KGF-increased cell motility was associated with increased fibronectin deposition during wound closure and with fibronectin reorganization into fibrils at the rear of the cells [16].

Analytical, diagnostic and therapeutic context of Fgf7

• In situ hybridization of the KGF-treated lungs revealed that the SP-C mRNA-expressing cells were arranged distally in the form of linear arrays, a pattern distinctly different from that in control lungs [22].
• By polymerase chain reaction, transcripts for both KGF and its receptor were detected early (rat gestational days 16 and 14, respectively) and their abundance increased during lung morphogenesis [22].
• Northern blot analysis showed higher expression of surfactant protein C (SP-C) mRNA (a marker for alveolar epithelial type II cells) in KGF-treated fetal lungs [22].
• Daily intravenous injection of KGF is also able to cause pneumocyte proliferation [23].
• Proliferating cell nuclear antigen immunohistochemistry confirmed the profound proliferative response induced by KGF [23].

References