The activin axis in liver biology and disease

Rodgarkia-Dara, Chantal; Vejda, Susanne; Erlach, Natascha; Losert, Annemarie; Bursch, Wilfried; Berger, Walter; Schulte‐Hermann, Rolf; Grusch, Michael

doi:10.1016/j.mrrev.2006.07.002

Cited by 94 publications

(87 citation statements)

References 140 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Blocking the activity of activin A with anti-activin A antibodies after CCl 4 treatment reduces the necrotic area and the secretion of serum transferases (22). However, activin A was also shown to induce the renewal of liver architecture by inducing collagen production in hepatic stellate cells (HSC) and tubulogenesis of LSECs (23,24). However, consistent with conflicting reports showing no effect of activin A on collagen production (24), we also did not observe significant effects of KLF2 on fibrosis (Fig.…”

Section: Discussionmentioning

confidence: 99%

Endothelial transcription factor KLF2 negatively regulates liver regeneration via induction of activin A

Manavski

Abel

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Endothelial cells (ECs) not only are important for oxygen delivery but also act as a paracrine source for signals that determine the balance between tissue regeneration and fibrosis. Here we show that genetic inactivation of flow-induced transcription factor Krüppel-like factor 2 (KLF2) in ECs results in reduced liver damage and augmentation of hepatocyte proliferation after chronic liver injury by treatment with carbon tetrachloride (CCl4). Serum levels of GLDH3 and ALT were significantly reduced in CCl4-treated EC-specific KLF2-deficient mice. In contrast, transgenic overexpression of KLF2 in liver sinusoidal ECs reduced hepatocyte proliferation. KLF2 induced activin A expression and secretion from endothelial cells in vitro and in vivo, which inhibited hepatocyte proliferation. However, loss or gain of KLF2 expression did not change capillary density and liver fibrosis, but significantly affected hepatocyte proliferation. Taken together, the data demonstrate that KLF2 induces an antiproliferative secretome, including activin A, which attenuates liver regeneration.

show abstract

Section: Discussionmentioning

confidence: 99%

Endothelial transcription factor KLF2 negatively regulates liver regeneration via induction of activin A

Manavski

Abel

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…phenobarbital) shifts the ratio between cell birth and cell death in favour of cell birth, in particular in preneoplastic lesions of rat liver; thereby, cancer development is accelerated. The opposite applies to feed restriction resulting in cancer prevention (for review: SchulteHermann et al, 1995;Rodgarkia-Dara et al, 2006). In addition, the treatment of rats with TGF-␤1 in vivo induced apoptosis in preneoplastic lesions of the liver, resulting in their rapid regression (Müllauer et al, 1996).…”

Section: Autophagy: Response To Metabolic Challenges Link To Nutritimentioning

confidence: 99%

Cell death and autophagy: Cytokines, drugs, and nutritional factors

Bursch¹,

Karwan²,

Mayer³

et al. 2008

Toxicology

Self Cite

117

View full text Add to dashboard Cite

Cells may use multiple pathways to commit suicide. In certain contexts, dying cells generate large amounts of autophagic vacuoles and clear large proportions of their cytoplasm, before they finally die, as exemplified by the treatment of human mammary carcinoma cells with the anti-estrogen tamoxifen (TAM, <= 1 mu M). Protein analysis during autophagic cell death revealed distinct proteins of the nuclear fraction including CST-pi and some proteasomal subunit constituents to be affected during autophagic cell death. Depending on the functional status of caspase-3, MCF-7 cells may switch between autophagic and apoptotic features of cell death [Fazi, B., Bursch, W., Fimia, G.M., Nardacci R., Piacentini, M., Di Sano, F., Piredda. L., 2008. Fenretinide induces autophagic cell death in caspase-defective breast cancer cells. Autophagy 4(4), 435-441]. Furthermore, the self-destruction of MCF-7 cells was found to be completed by phagocytosis of cell residues [Petrovski, G., Zahuczky, G., Katona, K., Vereb, G., Martinet. W., Nemes, Z., Bursch, W., Fesus, L., 2007. Clearance of dying autophagic cells of different origin by professional and non-professional phagocytes. Cell Death Diff. 14 (6),1117-1128]. Autophagy also constitutes a cell's strategy of defense upon cell damage by eliminating damaged bulk proteins/organelles. This biological condition may be exemplified by the treatment of MCF-7 cells with a necrogenic TAM-dose (10 mu M), resulting in the lysis of almost all cells within 24 h. However, a transient (1 h) challenge of MCF-7 cells with the same dose allowed the recovery of cells involving autophagy. Enrichment of chaperones in the insoluble cytoplasmic protein fraction indicated the formation of aggresomes, a potential trigger for autophagy. In a further experimental model HL60 cells were treated with TAM, causing dose-dependent distinct responses: 1-5 mu M TAM, autophagy predominant; 7-9 mu M, apoptosis predominant; 15 mu M, necrosis. These phenomena might be attributed to the degree of cell damage caused by tamoxifen, either by generating ROS, increasing membrane fluidity or forming DNA-adducts. Finally, autophagy constitutes a cell's major adaptive (survival) strategy in response to metabolic challenges such as glucose or amino acid deprivation, or starvation in general. Notably, the role of autophagy appears not to be restricted to nutrient recycling in order to maintain energy supply of cells and to adapt cell(organ) size to given physiological needs. For instance, using a newly established hepatoma cell line HCC-1.2, amino acid and glucose deprivation revealed a pro-apoptotic activity, additive to TGF-beta 1.The proapoptotic action of glucose deprivation was antagonized by 2-deoxyglucose, possibly by stabilizing the mitochondrial membrane involving the action of hexokinase II. These observations suggest that signaling cascades steering autophagy appear to provide links to those regulating cell number. Taken together, our data exemplify that a given cell may flexibly respond to type and degree of (micro)envir...

show abstract

“…Activin A acts as a potential anti-inflammatory cytokine, and is involved in the regulation of acute phase response in inflammatory diseases (4)(5)(6)(7)(8). Meanwhile, activin A is also a pro-inflammatory factor, which is involved in the pathogenesis of fibrotic human diseases (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

A Critical Role of Activin A in Maturation of Mouse Peritoneal Macrophages in vitro and in vivo

et al. 2009

View full text Add to dashboard Cite

Activin A, a multifunctional factor of the transforming growth factor-beta (TGF-) superfamily, is mainly produced by microglia and macrophages, and its anti-inflammatory and pro-inflammatory activities are both related to macrophage functions. However the direct effect of activin A on the rest macrophages in vivo remains unclear. In the present study, the results showed that activin A not only increased NO and IL-1 release, but also promoted phagocytic abilities of mouse peritoneal macrophages in vitro and in vivo, whereas it did not influence MHC I and MHC II expression. Moreover, we found that activin A significantly upregulated the expressions of CD14 and CD68, markers of mature macrophages, on the surface of macrophages in vitro and in vivo. These data suggest that activin A can induce primary macrophage maturation in vitro and in vivo, but may not trigger the acquired immune response via regulating expression of MHC molecules involved in presentation of antigen.

show abstract

The activin axis in liver biology and disease

Cited by 94 publications

References 140 publications

Endothelial transcription factor KLF2 negatively regulates liver regeneration via induction of activin A

Endothelial transcription factor KLF2 negatively regulates liver regeneration via induction of activin A

Cell death and autophagy: Cytokines, drugs, and nutritional factors

A Critical Role of Activin A in Maturation of Mouse Peritoneal Macrophages in vitro and in vivo

Contact Info

Product

Resources

About