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Roles of FGFs As Paracrine or Endocrine Signals in Liver Development, Health, and Disease.

Itoh N, Nakayama Y, Konishi M - Front Cell Dev Biol (2016)

Bottom Line: Serum FGF21 levels are elevated in non-alcoholic fatty liver.FGF21 also protects against non-alcoholic fatty liver.These findings provide new insights into the roles of FGFs in the liver and potential therapeutic strategies for hepatic disorders.

View Article: PubMed Central - PubMed

Affiliation: Medical Innovation Center, Kyoto University Graduate School of Medicine Kyoto, Japan.

ABSTRACT
The liver plays important roles in multiple processes including metabolism, the immune system, and detoxification and also has a unique capacity for regeneration. FGFs are growth factors that have diverse functions in development, health, and disease. The FGF family now comprises 22 members. Several FGFs have been shown to play roles as paracrine signals in liver development, health, and disease. FGF8 and FGF10 are involved in embryonic liver development, FGF7 and FGF9 in repair in response to liver injury, and FGF5, FGF8, FGF9, FGF17, and FGF18 in the development and progression of hepatocellular carcinoma. In contrast, FGF15/19 and FGF21 are endocrine signals. FGF15/19, which is produced in the ileum, is a negative regulator of bile acid metabolism and a stimulator of gallbladder filling. FGF15/19 is a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis. It is also required for hepatocellular carcinoma and liver regeneration. FGF21 is a hepatokine produced in the liver. FGF21 regulates glucose and lipid metabolism in white adipose tissue. Serum FGF21 levels are elevated in non-alcoholic fatty liver. FGF21 also protects against non-alcoholic fatty liver. These findings provide new insights into the roles of FGFs in the liver and potential therapeutic strategies for hepatic disorders.

No MeSH data available.


Related in: MedlinePlus

(A) Schematic representations of paracrine and endocrine FGF structures. SP, HB, and KLB indicate a secreted signal sequence, heparan sulfate-binding site, and Klotho-binding site, respectively. (B) Mechanisms of action of paracrine and endocrine FGFs. Paracrine FGFs are locally secreted signals that act on nearby target cells by diffusion, with functions in multiple developmental and physiological processes. Endocrine FGFs are secreted endocrine signals that act on distant target cells through the bloodstream, with functions in multiple metabolic processes. FGFR-HS and FGFR-Klotho indicate the FGFR-heparan sulfate complex and FGFR-Klotho complex, respectively.
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Figure 2: (A) Schematic representations of paracrine and endocrine FGF structures. SP, HB, and KLB indicate a secreted signal sequence, heparan sulfate-binding site, and Klotho-binding site, respectively. (B) Mechanisms of action of paracrine and endocrine FGFs. Paracrine FGFs are locally secreted signals that act on nearby target cells by diffusion, with functions in multiple developmental and physiological processes. Endocrine FGFs are secreted endocrine signals that act on distant target cells through the bloodstream, with functions in multiple metabolic processes. FGFR-HS and FGFR-Klotho indicate the FGFR-heparan sulfate complex and FGFR-Klotho complex, respectively.

Mentions: Paracrine FGFs, which comprise 15 members including FGF1-FGF6, FGF7-FGF10, FGF16-FGF18, FGF20, and FGF22, have a secreted signal sequence and heparan sulfate-binding site at their amino and carboxyl termini, respectively (Figures 1, 2A). Paracrine FGFs act on nearby target cells as locally secreted signals via diffusion. Heparan sulfate chains, which are long linear carbohydrate chains of repeating sulfated glucuronic acid linked to N-acetylglucosamine disaccharides, are covalently linked to specific cell surface transmembrane-type proteins. Heparan sulfate functions to sequester FGFs and modulate their diffusion. This modulation of diffusion directs paracrine FGFs as local signals (Figures 2B, 3; Goetz and Mohammadi, 2013; Ornitz and Itoh, 2015).


Roles of FGFs As Paracrine or Endocrine Signals in Liver Development, Health, and Disease.

Itoh N, Nakayama Y, Konishi M - Front Cell Dev Biol (2016)

(A) Schematic representations of paracrine and endocrine FGF structures. SP, HB, and KLB indicate a secreted signal sequence, heparan sulfate-binding site, and Klotho-binding site, respectively. (B) Mechanisms of action of paracrine and endocrine FGFs. Paracrine FGFs are locally secreted signals that act on nearby target cells by diffusion, with functions in multiple developmental and physiological processes. Endocrine FGFs are secreted endocrine signals that act on distant target cells through the bloodstream, with functions in multiple metabolic processes. FGFR-HS and FGFR-Klotho indicate the FGFR-heparan sulfate complex and FGFR-Klotho complex, respectively.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4829580&req=5

Figure 2: (A) Schematic representations of paracrine and endocrine FGF structures. SP, HB, and KLB indicate a secreted signal sequence, heparan sulfate-binding site, and Klotho-binding site, respectively. (B) Mechanisms of action of paracrine and endocrine FGFs. Paracrine FGFs are locally secreted signals that act on nearby target cells by diffusion, with functions in multiple developmental and physiological processes. Endocrine FGFs are secreted endocrine signals that act on distant target cells through the bloodstream, with functions in multiple metabolic processes. FGFR-HS and FGFR-Klotho indicate the FGFR-heparan sulfate complex and FGFR-Klotho complex, respectively.
Mentions: Paracrine FGFs, which comprise 15 members including FGF1-FGF6, FGF7-FGF10, FGF16-FGF18, FGF20, and FGF22, have a secreted signal sequence and heparan sulfate-binding site at their amino and carboxyl termini, respectively (Figures 1, 2A). Paracrine FGFs act on nearby target cells as locally secreted signals via diffusion. Heparan sulfate chains, which are long linear carbohydrate chains of repeating sulfated glucuronic acid linked to N-acetylglucosamine disaccharides, are covalently linked to specific cell surface transmembrane-type proteins. Heparan sulfate functions to sequester FGFs and modulate their diffusion. This modulation of diffusion directs paracrine FGFs as local signals (Figures 2B, 3; Goetz and Mohammadi, 2013; Ornitz and Itoh, 2015).

Bottom Line: Serum FGF21 levels are elevated in non-alcoholic fatty liver.FGF21 also protects against non-alcoholic fatty liver.These findings provide new insights into the roles of FGFs in the liver and potential therapeutic strategies for hepatic disorders.

View Article: PubMed Central - PubMed

Affiliation: Medical Innovation Center, Kyoto University Graduate School of Medicine Kyoto, Japan.

ABSTRACT
The liver plays important roles in multiple processes including metabolism, the immune system, and detoxification and also has a unique capacity for regeneration. FGFs are growth factors that have diverse functions in development, health, and disease. The FGF family now comprises 22 members. Several FGFs have been shown to play roles as paracrine signals in liver development, health, and disease. FGF8 and FGF10 are involved in embryonic liver development, FGF7 and FGF9 in repair in response to liver injury, and FGF5, FGF8, FGF9, FGF17, and FGF18 in the development and progression of hepatocellular carcinoma. In contrast, FGF15/19 and FGF21 are endocrine signals. FGF15/19, which is produced in the ileum, is a negative regulator of bile acid metabolism and a stimulator of gallbladder filling. FGF15/19 is a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis. It is also required for hepatocellular carcinoma and liver regeneration. FGF21 is a hepatokine produced in the liver. FGF21 regulates glucose and lipid metabolism in white adipose tissue. Serum FGF21 levels are elevated in non-alcoholic fatty liver. FGF21 also protects against non-alcoholic fatty liver. These findings provide new insights into the roles of FGFs in the liver and potential therapeutic strategies for hepatic disorders.

No MeSH data available.


Related in: MedlinePlus