Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Iroquois homeobox (Irx5) gene is essential in embryonic development and cardiac electrophysiology. Although recent studies have reported that IRX5 protein is involved in regulation of the cell cycle and apoptosis in prostate cancer cells, little is known about the role of IRX5 in the adult vasculature. Here we report novel observations on the role of IRX5 in adult vascular smooth muscle cells (VSMCs) during proliferation in vitro and in vivo. Comparative studies using primary human endothelial cells, VSMCs, and intact carotid arteries to determine relative expression of Irx5 in the peripheral vasculature demonstrate significantly higher expression in VSMCs. Sprague-Dawley rat carotid arteries were subjected to balloon catherization, and the presence of IRX5 was examined by immunohistochemistry after 2 wk. Results indicate markedly elevated IRX5 signal at 14 days compared with uninjured controls. Total RNA was isolated from injured and uninjured arteries, and Irx5 expression was measured by RT-PCR. Results demonstrate a significant increase in Irx5 expression at 3-14 days postinjury compared with controls. Irx5 genetic gain- and loss-of-function studies using thymidine and 5-bromo-2'-deoxyuridine incorporation assays resulted in modulation of DNA synthesis in primary rat aortic VSMCs. Quantitative RT-PCR results revealed modulation of cyclin-dependent kinase inhibitor 1B (p27(kip1)), E2F transcription factor 1 (E2f1), and proliferating cell nuclear antigen (Pcna) expression in Irx5-transduced VSMCs compared with controls. Subsequently, apoptosis was observed and confirmed by morphological observation, caspase-3 cleavage, and enzymatic activation compared with control conditions. Taken together, these results indicate that Irx5 plays an important role in VSMC G1/S-phase cell cycle checkpoint control and apoptosis.
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PMID:Iroquois homeobox transcription factor (Irx5) promotes G1/S-phase transition in vascular smooth muscle cells by CDK2-dependent activation. 2717 Jun 37

Previously, our transcriptome sequencing revealed that lnc9141 was differentially expressed in muscles of fetal bovine, calf, and adult bovine, which is considered to provide the basis for raising the muscle mass. In this study, we identified lnc9141 characters. lnc9141 has different transcription start sites and 3' alternative splicing sites of exon 1, producing lnc9141-a and lnc9141-b transcripts that were highly expressed in the heart and lung. Moreover, neither lnc9141-a nor lnc9141-b had the ability to encode proteins. The functions of lnc9141-a and lnc9141-b were explored by cell cycle, 5-ethynyl-2'-deoxyuridine (EdU), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results showed that lnc9141-a or lnc9141-b overexpression decreased the number of myoblasts in the S phase and increased the proportion of cells in the G0/G1 phase. Furthermore, overexpressing lnc9141-a and lnc9141-b respectively downregulated the expression of Cyclin D1. However, lnc9141-a or lnc9141-b interference was found to increase the number of S-phase myoblasts, and upregulate Cyclin D1 and Cyclin E expression. Through Annexin V-FITC/propidium iodide (PI) double staining and the expression of apoptosis marker genes (Bax, Bcl2, and Caspase-3), it was found that lnc9141-b could regulate the expression of Bax gene. Meantime, high expression of lnc9141-b could decrease MyHC expression. In addition, the intergenic region between lnc9141 and IRX5 was 2.3 kb, with a head-to-head orientation. The study also revealed the core regions of the lnc9141 and IRX5 promoter. Our study demonstrated that both lnc9141-a and -b expression inhibited bovine myoblast proliferation. However, lnc9141-b regulated Bax and MyHC expression. The regulatory mechanism of lnc9141-a and lnc9141-b needs to be further explored.
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PMID:lnc9141-a and -b Play a Different Role in Bovine Myoblast Proliferation, Apoptosis, and Differentiation. 3167 68