FGF-10 Is a Growth Factor for Preadipocytes in White Adipose Tissue

Yamasaki, Masahiro; Emoto, Hisayo; Konishi, Morichika; Mikami, Tadahisa; Ohuchi, Hideyo; Nakao, Kazuwa; Itoh, Nobuyuki

doi:10.1006/bbrc.1999.0594

Cited by 45 publications

(33 citation statements)

References 23 publications

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“…These findings, together with the results presented here, suggest that FGF-7 acts specifically on epithelial cells, whereas FGF-10 seems to have a broader cell type specificity. This is further supported by the demonstration that FGF-10 is mitogenic for primary rat preadipocytes (46). The mitogenicity of FGF-10 for mesenchymal cells in vivo is unclear, because fairly high concentrations of the ligand are required for this effect.…”

Section: Discussionmentioning

confidence: 87%

Fibroblast Growth Factor (FGF) Receptor 1-IIIb Is a Naturally Occurring Functional Receptor for FGFs That Is Preferentially Expressed in the Skin and the Brain

Beer¹,

Vindevoghel²,

Gait³

et al. 2000

Journal of Biological Chemistry

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Fibroblast growth factors (FGFs) 1 comprise a growing family of structurally conserved mitogens, which currently includes 19 different members (1-10). With the exception of FGF-7, which appears to act specifically on epithelial cells (11), most members of the FGF family are broad-spectrum mitogens, and several also stimulate various processes such as cell migration, angiogenesis, neurite outgrowth, and neuroprotection (12). FGFs interact with three different types of binding proteins. These include a cystein-rich receptor of as yet unknown function, which binds various types of FGFs with high affinity (13), and heparan sulfate proteoglycans, which bind FGFs with low affinities, although this interaction is essential for the binding of these factors to their high-affinity receptors (12). There are four different genes encoding high-affinity transmembrane receptors. These receptors, designated as FGF receptors 1 to 4 (FGFR1-4), are characterized by the presence of two or three immunoglobulin (Ig)-like domains in the extracellular region and a tyrosine kinase domain in the intracellular region of the receptor (14). They are responsible for FGF-mediated signal transduction (14). Additional diversity in the FGF receptor family is generated by alternative splicing. Of particular importance are splice variants that differ in the second half of the third Ig-like domain, since these variants differ in their ligand binding specificity (15-17). Thus two transmembrane receptor variants have been identified for FGFR2 that were designated FGFR2-IIIb and FGFR2-IIIc. Whereas the IIIb variant of FGFR2 binds FGF-1, -3, -7, and -10 with appreciable affinity (15, 19 -21), the IIIc variant is a high-affinity receptor for 20). By analogy to FGFR2, IIIb and IIIc splice variants have also been identified for FGFR3 (17), whereas this type of alternative splicing does not occur with the FGFR4 transcripts (22). Interestingly, three different exons (designated IIIa, IIIb and IIIc) that might encode possible alternatives within the third Ig-like domain are present in both the human and murine FGFR1 genes, and receptors including the IIIa and the IIIc exon have been identified (23). The receptor that contains exclusively the IIIa exon is a soluble variant, which binds FGF-2 with higher affinity than FGF-1 (24). FGFR1-IIIc is a transmembrane receptor that binds . By contrast, a full-length receptor cDNA, which includes sequences encoding the IIIb exon of FGFR1 has as yet not been isolated. However, mRNAs encoding the FGFR1-IIIb exon have been found in mice and humans using RNase protection assays and reverse transcriptase polymerase chain reaction (16,23). These mRNAs encode the complete extracellular domain of FGFR1-IIIb, but it has as yet not been possible to demonstrate the presence of sequences encoding the intracellular domain. Thus it has been unclear whether FGFR1-IIIb is a soluble or a transmembrane receptor and whether it is a functional receptor for FGFs. To gain some insight into the properties of a putative FGFR1-IIIb, we had prev...

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Section: Discussionmentioning

confidence: 87%

Fibroblast Growth Factor (FGF) Receptor 1-IIIb Is a Naturally Occurring Functional Receptor for FGFs That Is Preferentially Expressed in the Skin and the Brain

Beer¹,

Vindevoghel²,

Gait³

et al. 2000

Journal of Biological Chemistry

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“…Also, a role for FGFs in human adipose tissue metabolism is suggested by the observation that preadipocytes from massively obese individuals have much higher expression of FGF-2 than the same cells from lean counterparts (45). The fact that human adipose tissue expresses members of the FGF family, including their cognate receptors, provides further support for a metabolic role of these growth factors in human adipose tissue (18,40).…”

Section: Fgf-1: Key Regulator Of Human Adipogenesismentioning

confidence: 98%

“…Although both positive and negative effects have been reported for different family members, including FGF-1 and -2 (34), in general these growth factors are reported to have a mitogenic effect on preadipocytes while having no effect or even potently inhibiting their differentiation (35)(36)(37)(38)(39)(40)(41)(42). In contrast to previous studies, where exposure to FGF-1 was restricted to relatively short periods during either growth or differentiation, we have cultured cells in the presence of FGF-1 for sustained periods (1-2 months).…”

Section: Fgf-1: Key Regulator Of Human Adipogenesismentioning

confidence: 99%

Fibroblast Growth Factor 1

et al. 2004

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Obesity, with its related problems, is recognized as the fastest growing disease epidemic facing the world, yet we still have limited insight into the regulation of adipose tissue mass in humans. We have previously shown that adipose-derived microvascular endothelial cells (MVECs) secrete a factor(s) that increases proliferation of human preadipocytes. We now demonstrate that coculture of human preadipocytes with MVECs significantly increases preadipocyte differentiation, evidenced by dramatically increased triacylglycerol accumulation and glycerol-3-phosphate dehydrogenase activity compared with controls. Subsequent analysis identified fibroblast growth factor (FGF)-1 as an adipogenic factor produced by MVECs. Expression of FGF-1 was demonstrated in MVECs but not in preadipocytes, while preadipocytes were shown to express FGF receptors 1-4. The proliferative effect of MVECs on human preadipocytes was blocked using a neutralizing antibody specific for FGF-1. Pharmacological inhibition of FGF-1 signaling at multiple steps inhibits preadipocyte replication and differentiation, supporting the key adipogenic role of FGF-1. We also show that 3T3-L1 cells, a highly efficient murine model of adipogenesis, express FGF-1 and, unlike human preadipocytes, display no increased differentiation potential in response to exogenous FGF-1. Conversely, FGF-1-treated human preadipocytes proliferate rapidly and differentiate with high efficiency in a manner characteristic of 3T3-L1 cells. We therefore suggest that FGF-1 is a key human adipogenic factor, and these data expand our understanding of human fat tissue growth and have significant potential for development of novel therapeutic strategies in the prevention and management of human obesity. Diabetes 53: [3097][3098][3099][3100][3101][3102][3103][3104][3105][3106] 2004

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“…2). Fgf10 is known to be expressed by adipocyte precursors and Fgf10-null neonates suffer from impaired development of the white adipose tissue (Sakaue et al, 2002;Yamasaki et al, 1999). Thus, we decided to investigate whether Fgf10-positive cells give rise to an adipose-related cell lineage in the lung, the lipofibroblasts.…”

Section: Fgf10-positive Cells Are Progenitors For Parabronchial and Vmentioning

confidence: 99%

Fgf10-positive cells represent a progenitor cell population during lung development and postnatally

et al. 2014

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FGF-10 Is a Growth Factor for Preadipocytes in White Adipose Tissue

Cited by 45 publications

References 23 publications

Fibroblast Growth Factor (FGF) Receptor 1-IIIb Is a Naturally Occurring Functional Receptor for FGFs That Is Preferentially Expressed in the Skin and the Brain

Fibroblast Growth Factor (FGF) Receptor 1-IIIb Is a Naturally Occurring Functional Receptor for FGFs That Is Preferentially Expressed in the Skin and the Brain

Fibroblast Growth Factor 1

Fgf10-positive cells represent a progenitor cell population during lung development and postnatally

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