Anti-Acvr2a polyclonal antibody

Growth differentiation factor 8 (GDF8), also known as myostatin, is highly expressed in the mammalian musculoskeletal system and plays critical roles in the regulation of skeletal muscle growth. Though not exclusively expressed in the musculoskeletal system, the expression and biological function of GDF8 has never been examined in the human ovary. Pentraxin 3 (PTX3) plays a key role in the assembly of extra-cellular matrix, which is essential for cumulus expansion, ovulation and in vivo fertilization. The aim of this study was to investigate GDF8 expression and function in human granulosa cells and to examine its underlying molecular determinants. An established immortalized human granulosa cell line (SVOG), granulosa cell tumor cell line (KGN) and primary granulosa-lutein cells were used as study models. We now demonstrate for the first time that GDF8 is expressed in human granulosa cells and follicular fluid. All 16 follicular fluid samples tested contained GDF8 protein at an average concentration of 3 ng/ml. In addition, GDF8 treatment significantly decreased PTX3 mRNA and protein levels. These suppressive effects, along with the induction of SMAD2/3 phosphorylation, were abolished by co-treatment with the ALK4/5/7 inhibitor SB431542. Knockdown of ALK5, ACVR2A/ACVR2B or SMAD4 reversed the effects of GDF8-induced PTX3 suppression. These results indicate that GDF8 down-regulates PTX3 expression via ACVR2A/ACVR2B-ALK5-mediated SMAD-dependent signaling in human granulosa cells. These novel findings support a potential role for GDF8 in the regulation of follicular function, likely via autocrine effects on human granulosa cells. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Administration of human bone marrow-derived mesenchymal stem cells (BM-MSCs) significantly alleviates allergic airway inflammation. There are no studies that refer to the role of microRNAs (miRNAs) after the BM-MSCs treatment in airway allergic inflammation. We induced a mouse model of asthma and performed the transplantation of BM-MSCs. We analyzed aberrant miRNAs and key immune regulators using both miRNA and messenger RNA (mRNA) polymerase chain reaction (PCR) arrays. We identified that 296 miRNAs were differently expressed after the induction of asthma and/or the treatment of BM-MSCs, in which 14 miRNAs presented the reverse variation tendency between asthma induction and BM-MSCs transplantation. Mmu-miR-21a-3p, mmu-miR-449c-5p, and mmu-miR-496a-3p were further confirmed to be differently expressed with additional samples and quantitative real-time PCR. With an mRNA PCR array, we identified 19 genes to be involved in the allergy induction and the administration of BM-MSCs. Further target genes analysis revealed that mmu-miR-21a-3p was significantly correlated with the immune regulator activin Areceptor, Type IIA(Acvr2a). Mmu-miR-21a-3p had opposite expression with Acvr2a after asthma and BM-MSCs treatment. Acvr2a had binding sites for miR-21a for bothmice and human, suggesting that miR-21/Acvr2a axis is conserved between human and mice. Dual-luciferase reporter assay showed that mmu-miR-21a-3p negatively regulated the transcript of Acvr2a. In addition, has-miR-21a inhibitor significantly increased the expression of Acvr2a mRNA in BEAS-2B cells under lipopolysaccharide stimulation. Our results suggest that there were different miRNA and mRNA profiles after asthma induction and BM-MSCs treatment, and the miR-21/Acvr2a axis is an important mechanism for the induction of asthmatic inflammation.