Differential regulated expression of keratinocyte growth factor and its receptor in experimental and human liver fibrosis

Otte, Jan-Michel; Schwenger, Martin; Brunke, Gabriele; Schmitz, Frank; Otte, C.; Kiehne, Karlheinz; Kloehn, Sievert; Mönig, H.; Schmidt, Wolfgang E.; Herzig, Karl‐Heinz

doi:10.1016/j.regpep.2007.06.007

Cited by 7 publications

(9 citation statements)

References 33 publications

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“…In addition, high expression of FGF7 in patients with chronic liver diseases (Steiling et al 2004;Otte et al 2007) and in experimental rat models of hepatic fibrosis (Murakami et al 2011) were previously reported. Thus, we predict that LPCs are regulated through the same mechanism in humans as in rodents.…”

Section: Discussionmentioning

confidence: 87%

FGF7 is a functional niche signal required for stimulation of adult liver progenitor cells that support liver regeneration

et al. 2013

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The liver is a unique organ with a remarkably high potential to regenerate upon injuries. In severely damaged livers where hepatocyte proliferation is impaired, facultative liver progenitor cells (LPCs) proliferate and are assumed to contribute to regeneration. An expansion of LPCs is often observed in patients with various types of liver diseases. However, the underlying mechanism of LPC activation still remains largely unknown. Here we show that a member of the fibroblast growth factor (FGF) family, FGF7, is a critical regulator of LPCs. Its expression was induced concomitantly with LPC response in the liver of mouse models as well as in the serum of patients with acute liver failure. Fgf7-deficient mice exhibited markedly depressed LPC expansion and higher mortality upon toxin-induced hepatic injury. Transgenic expression of FGF7 in vivo led to the induction of cells with characteristics of LPCs and ameliorated hepatic dysfunction. We revealed that Thy1 + mesenchymal cells produced FGF7 and appeared in close proximity to LPCs, implicating a role for those cells as the functional LPC niche in the regenerating liver. These findings provide new insights into the cellular and molecular basis for LPC regulation and identify FGF7 as a potential therapeutic target for liver diseases.

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Section: Discussionmentioning

confidence: 87%

FGF7 is a functional niche signal required for stimulation of adult liver progenitor cells that support liver regeneration

et al. 2013

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“…In detail, the male Wistar rats were exposed to phenobarbitone and CCl 4 for up to 70 days. In congruence with the human clinical data, IHC of liver sections from the treated rats revealed that FGF7 was exclusively expressed in myofibroblasts in fibrotic foci with isolated protein and mRNA levels of FGF7 positively correlated to fibrosis severity [ 27 ]. The function of HSC-derived FGF7 has been explored in a mouse partial hepatectomy model [ 28 ].…”

Section: Autocrine and Paracrine Actions Of Fgfs On Hscsmentioning

confidence: 91%

“…The production of FGF7 by HSCs during liver injury has also been investigated. In two human studies, livers were collected from patients with cirrhosis, hepatitis B and hepatitis C (HBV, HCV), autoimmune hepatitis, and alcohol induced liver damage [ 26 , 27 ]. Both studies found that FGF7 was expressed in fibrotic livers but not in healthy control liver samples.…”

Section: Autocrine and Paracrine Actions Of Fgfs On Hscsmentioning

confidence: 99%

“…Steiling et al noted that the fibrosis staging in HCV patients was positively correlated with FGF7 mRNA levels and immunohistochemistry (IHC) of the liver showed that FGF7 expression colocalized with α SMA [ 26 ]. Otte et al also included an animal study parallel to their clinical investigation [ 27 ]. In detail, the male Wistar rats were exposed to phenobarbitone and CCl 4 for up to 70 days.…”

Section: Autocrine and Paracrine Actions Of Fgfs On Hscsmentioning

confidence: 99%

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Regulation of Hepatic Stellate Cells and Fibrogenesis by Fibroblast Growth Factors

Schumacher

Guo

2016

BioMed Research International

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Fibroblast growth factors (FGFs) are a family of growth factors critically involved in developmental, physiological, and pathological processes, including embryogenesis, angiogenesis, wound healing, and endocrine functions. In the liver, several FGFs are produced basally by hepatocytes and hepatic stellate cells (HSCs). Upon insult to the liver, expression of FGFs in HSCs is greatly upregulated, stimulating hepatocyte regeneration and growth. Various FGF isoforms have also been shown to directly induce HSC proliferation and activation thereby enabling autocrine and paracrine regulation of HSC function. Regulation of HSCs by the endocrine FGFs, namely, FGF15/19 and FGF21, has also recently been identified. With the ability to modulate HSC proliferation and transdifferentiation, targeting FGF signaling pathways constitutes a promising new therapeutic strategy to treat hepatic fibrosis.

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“…Previous studies on the molecular mechanism underlying the development of cirrhosis have shown that keratinocyte growth factor (KGF) [10], which is predominantly produced and secreted by hepatic stellate cells (HSCs) [11], plays a critical role in the prevention of cirrhosis and enhancement of liver regeneration [11,12]. KGF is a member from fibroblast growth factor (FGF) family and is known as FGF7 [10].…”

Section: Introductionmentioning

confidence: 99%

Suppression of MicroRNA-219-5p Activates Keratinocyte Growth Factor to Mitigate Severity of Experimental Cirrhosis

Chen

Cui²,

Feng³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Keratinocyte growth factor (KGF) plays a critical role in prevention of cirrhosis and enhancement of liver regeneration. However, the molecular regulation of KGF in liver is unknown. MicroRNAs (miRNAs) control the pathogenesis of cirrhosis, whereas the exact involved miRNAs and molecular signaling pathways remain ill-defined. Here we addressed these questions. Methods: We examined the correlation of the levels of miR-219-5p and KGF in the liver biopsies from patients with liver diseases. The effects of overexpression or suppression of miR-219-5p on KGF were examined in both human and mouse hepatic stellate cells (HSCs). Bioinformatics analysis was applied to examine the binding of human/mouse miR-219-5p to the 3'-UTR of human/mouse KGF mRNA, respectively. Finally, adeno-associated viruses carrying antisense of miR-219-5p were infused into the liver from the mice that had developed cirrhosis by carbon tetrachloride (CCl₄), and the effects on KGF levels and liver damage and function were examined. Results: The levels of miR-219-5p and KGF in the liver biopsies were inversely correlated. MiR-219-5p inhibited KGF expression in both human and mouse HSCs, through directly binding the 3'-UTR of KGF mRNA. Expression of antisense of miR-219-5p significantly attenuated the levels of liver fibrosis, portal hypertension and sodium retention caused by CCl₄. Conclusions: Suppression of miR-219-5p may benefit the liver regeneration and prevent cirrhosis through increasing KGF.

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Differential regulated expression of keratinocyte growth factor and its receptor in experimental and human liver fibrosis

Cited by 7 publications

References 33 publications

FGF7 is a functional niche signal required for stimulation of adult liver progenitor cells that support liver regeneration

FGF7 is a functional niche signal required for stimulation of adult liver progenitor cells that support liver regeneration

Regulation of Hepatic Stellate Cells and Fibrogenesis by Fibroblast Growth Factors

Suppression of MicroRNA-219-5p Activates Keratinocyte Growth Factor to Mitigate Severity of Experimental Cirrhosis

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