Development of preventive for periodontitis by using avtivin that indices apoptosis and suppresses the production of IL-1

点击翻译按钮获取中文摘要

Activins transduce their signals through binding to activin type I receptor (ActR-I) and activin type II receptor (ActR-II), both containing a serine/threonine kinase domain. In this study, we have clarified the role of activin type I receptors in activin A signaling for growth inhibition in HS-72 mouse B cell hybridoma cells. Overexpression of ActR-I suppressed activin A-induced cell cycle arrest in the G1 phase caused by inhibiting Rb phosphorylation through inducting p21^<CIP1/WAF1> and subsequent apoptosis. In contrast, HS-72 cells that overexpressed ActR-IB facilitated activin A-induced apoptosis. These findings suggest that the ActR-I/ActR-IB expression ratio could regulate cell cycle arrest in the G1 phase and subsequent apoptosis in HS-72 cells induced by activin A.Recently, Activins were found to relay signals from serine/threonine kinase receptors in membrane to nucleus via intracellular Sma-and Mad-related (Smad) proteins. Inhibitory Smad proteins are known to prevent the interaction between the serine/threonine kinase receptors and pathway-restricted Smad proteins. Smad7 was identified as a TGF-beta-inducible antagonist of TGF-beta signaling. In this study, we found that the mRNA expression of Smad7 was induced by activin A in HS-72 cells. The ectopic expression of mouse Smad7 in HS-72 cells suppressed the activin A-induced cell-cycle arrest in the G1 phase by abolishing the activin A-induced expression of p21^<CIP1/WAF1> and hypophosphorylation of retinoblastoma protein.Furthermore, Smad7 expression suppressed activin A-induced apoptosis in HS-72 cells. Thus, our data indicate that Smad7 is an activin A-inducible antagonist of activin A-induced growth arrest and apoptosis of B lineage cells.