Regulation of activin receptor-interacting protein 2 expression in mouse hepatoma Hepa1-6 cells and its relationship with collagen type IV

Abstract

AIM:To investigate the regulation of activin receptorinteracting protein 2 (ARIP2) expression and its possible relationships with collagen type Ⅳ (collagen Ⅳ) in mouse hepatoma cell line Hepal-6 cells. METHODS:The ARIP2 mRNA expression kinetics in Hepal-6 cells was detected by RT-PCR, and its regulation fa c t o r s w e re a n a l y ze d by t re a t m e n t w i t h s i g n a l transduction activators such as phorbol 12-myristate 13-acetate (PMA), forskolin and A23187. After pcDNA3-ARIP2 was transfected into Hepal-6 cells, the effects of ARIP2 overexpression on activin type Ⅱ receptor (ActRII) and collagen Ⅳ expression were evaluated. RESULTS:The expression levels of ARIP2 mRNA in Hapel-6 cells were elevated in time-dependent manner 12 h after treatment with activin A and endotoxin LPS, but not changed evidently in the early stage of stimulation (2 or 4 h). The ARIP2 mRNA expression was increased after stimulated with signal transduction activators such as PMA and forskolin in Hepal-6 cells, whereas decreased after treatment with A23187 (25.3% ± 5.7% vs 48.1% ± 3.6%, P < 0.01). ARIP2 overexpression could remarkably suppress the expression of ActRIIA mRNA in dose-dependent manner, but has no effect on ActRIIB in Hepal-6 cells induced by activin A. Furthermore, we have found that overexpression of ARIP2 could inhibit collagen Ⅳ mRNA and protein expressions induced by activin A in Hapel-6 cells. CONCLUSION:

Localisation and Role of Activin Receptor‐Interacting Protein 1 in Mouse Brain

“…Activin A is widely produced and plays important roles in various tissues , such as in hypothalamic neuroendocrinological and feeding‐related systems, as well as in cortical and limbic pathways, as a neuromodulator or for maintenance of neurones . Activin receptors are transmembrane proteins, have the serine/threonine kinase domain in their cytoplasmic regions and are widely distributed in various tissues.…”

Activins and activin antagonists in hepatocellular carcinoma

“…ARIPS 1 and 2 (activin receptor-interacting proteins) are PDZ (PSD-95/Discs-large/ZO-1) protein-protein interaction domain-containing proteins that were described to interact with type Ⅱ activin receptors and inhibit or augment activin signaling, depending on the isoforms expressed [136][137][138] . ARIP 2 was recently shown to be induced by activin A in the mouse hepatoma cell line Hepa1-6 and to decrease activin-mediated collagen Ⅳ expression, suggesting that it participates in a negative feedback regulation of activin-induced liver fibrosis [139] . Data with regard to a role of ARIPS in HCC or other tumor types are missing so far.…”

Ramipril attenuates left ventricular remodeling by regulating the expression of activin A-follistatin in a rat model of heart failure

“…In particular, activin A is associated with fibrosis, with several experiments confirming that activin A is an important factor of inducing fibrosis of liver of animals 1 2 3 . Follistatin (FS) is an activin-binding protein that is measurable in extracellular matrix and serum 4 5 . When Activins bind to FS, the complex is internalized by endocytosis and are subsequently degraded by proteolysis 6 .…”