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Genetics of muscle mass and strength
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Stephen M. Roth, Henning Wackerhage
The researchers used a linkage analysis to further refine the regions identified in their previous studies and so far, have identified the activin receptor 1B (ACVR1B) related to muscle strength (34). Examination of this gene in a transgenic mouse model would be a possible next step to better understand the implications of variation in this gene for muscle traits, but only limited work in this area has been performed to date. This gene is related to the myostatin pathway which we discuss in Chapter 8 as a potential regulator of the adaptation to resistance exercise.
Herpesvirus microRNAs for Use in Gene Therapy Immune-Evasion Strategies
Published in Yashwant Pathak, Gene Delivery, 2022
Vineet Mahajan, Shruti Saptarshi, Yashwant Pathak
This section highlights the regulatory strategies and targets of HCMV encoded miRNAs. Cytokine regulation by HCMV miRNA (miR-UL148D-1) was demonstrated for ACVR1B gene to limit IL-6 and RANTES/CCL5 secretion.31 Similarly, the HCMV miRs UL112-3p, US5-1, UL112-1, US25-1-5p, and UL148D target multiple host inflammatory genes, with the result of mitigation of inflammatory response. Furthermore, miR-UL112-3p was shown to target the TLR2 transcript to limit signaling through the TLR2-IRAK1 axis and block NFκB activation.29 Although some HCMV miRNAs and their targets have been reported, many more miRNAs, their target antiviral mechanisms, and their biological functions still remain unclear. A recent study reported for the first time the role of HCMV miRNA hcmv-miR-US33as-5p in targeting the IFN signaling pathway during both lytic and latent infection.32
TGF-β signaling in testicular development, spermatogenesis, and infertility
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Poonam Mehta, Meghali Joshi, Rajender Singh
Inhibin-α deficiency is associated with testicular tumors, because inhibin and FSH levels are inversely related and FSH regulates the gonadal cell proliferation (89). Recently, transcriptome analysis studies in seminomas and of TCam-2 seminoma model cell line revealed the potentially active pathways. Combined datasets from Affymetrix microarrays and RNAseq analysis revealed the presence of transcript levels of TGF-β signaling. GDF3, GDF11 and BMP7 transcripts were consistently detected in seminomas and TCam-2. Transcripts encoding receptor proteins such as ACVR1A and ACVR1B, ACVR2A and ACVR2B were also detected at high levels (90).
Differential expression of BMP/SMAD signaling and ovarian-associated genes in the granulosa cells of FecB introgressed GMM sheep
Published in Systems Biology in Reproductive Medicine, 2020
Satish Kumar, Pradeep Kumar Rajput, Sangharatna V. Bahire, Basanti Jyotsana, Vijay Kumar, Davendra Kumar
It is well known that the BMP factors (ligands) act through the two sub-types of receptors with serine/threonine kinase activity. Seven type I receptors and five type II serine/threonine kinase receptors have been reported (Attisano and Wrana 1996). Activin receptor-like kinase 1 (Alk1 or ACVRL1), Alk2 (ACVR1), Alk3 (BMPR1A), Alk4 (ACVR1B), Alk5 (TGFβR1), Alk6 (BMPR1B), and Alk7 (ACVR1C) act as type 1 receptors, whereas BMP receptor 2 (BMPRII), Activin receptor 2 (ActR2), Activin receptor 2A/Activin receptor 2B (ActR2A/2B), and TGFβ receptor 2 (TGFβRII) are the type 2 receptors (Kaivo-oja et al. 2006; Loomans and Andl 2016). Out of seven type 1 receptors, three receptors bind and interact with BMP ligands; BMPR1A, BMPR1B, and ActR1A (Horbelt et al. 2012). Out of five type 2 receptors, three receptors are known to interact with BMP ligands; BMPRII, ActR2A, and ActR2B (Wang et al. 2014). These BMP factors interact with hetero-tetrameric complexes of type 1 and type 2 receptors. Type 2 receptor phosphorylates the type 1 receptor. Once phosphorylated, the type 1 receptor phosphorylates one of the receptor-regulated intracellular signaling SMAD proteins (either SMAD1, -5 and -8). Hence, the phosphorylated BMP receptor-regulated SMADs hetero-dimerizes with common SMAD4 and translocate into the nucleus, where these hetero-complexes act as a transcriptional activator to regulate the expression of the target genes (Massagué 1998, 2000; Souza et al. 2004). Interaction of the BMP, TGFβ, and GDF ligands to their respective receptors have been mentioned in Figure 1A-C.
The role of miRNA-210 in pre-eclampsia development
Published in Annals of Medicine, 2022
Ilona Jaszczuk, Dorota Koczkodaj, Adrianna Kondracka, Anna Kwaśniewska, Izabela Winkler, Agata Filip
In an attempt to find further correlations between the miR-210 expression level and the severity of the clinical course of pre-eclampsia. Jairajpuri et al. [47] selected 2 genes ACVR1B and ADAM-17, the down-regulation of which occurred in severe PE and was not recorded in mild PE. ACVR1B (activin A receptor type 1B) encodes the receptor complex with activin involved, inter alia, in the production of extracellular matrix and immunosuppression [46,47]. ADAM-17 is a metalloproteinase domain gene involved in regulating the activity of placental cells.
Identification of novel autoantibodies based on the protein chip encoded by cancer-driving genes in detection of esophageal squamous cell carcinoma
Published in OncoImmunology, 2020
Guiying Sun, Hua Ye, Xiao Wang, Lin Cheng, Pengfei Ren, Jianxiang Shi, Liping Dai, Peng Wang, Jianying Zhang
Based on the customized protein chip of cancer-driving genes and ELISA, ten autoantibodies (GNA11, SRSF2, GNAS, PDGFRA, PTEN, P53, ACVR1B, CASP8, DAXX, and MEN1) related to the diagnosis of ESCC were identified in this study. The genes encoding the first three proteins are carcinogenic genes, and the last six genes are tumor suppressor genes. GNA11 belongs to the family of guanine nucleotide-binding proteins (G proteins), which function as modulators or transducers in various transmembrane signaling systems.29 SRSF2 is a member of the serine/arginine (SR)-rich family of pre-mRNA splicing factors and involved in regulating cell proliferation and maintaining genomic stability.30 GNAS is a complex imprinted expression gene and an important component of many signal transduction pathways, such as APC, PI3K, TGF-b, and RAS pathway.31 PDGFRA is closely related to the invasion and malignant transformation of tumors. Immunochemical analysis showed that PDGFRA was positive in a rare case of primary small cell carcinoma of the esophagus.32 PTEN is involved in a variety of cell signal transduction pathways, including regulation of cell growth, migration, apoptosis, and maintenance of chromosomal integrity.33,34 The mutation of TP53 can acquire carcinogenic characteristics and promote the invasion, metastasis, proliferation, and survival of cancer cells. Wu et al. reported that the positive rate of anti-P53 autoantibody in serum of cancer patients was significantly higher than that of healthy controls (14.59% vs 1.02%), which suggested that anti-P53 autoantibody can be used to detect malignant tumors.35 ACVR1B, an activin sensor, belongs to the transforming growth factor beta (TGF-beta) superfamily and is involved in regulating muscle growth.36 CASP8 is involved in exogenous apoptotic signaling pathway, and its genetic variation can affect cancer susceptibility.37 DAXX can bind to the death domain of Fas death receptor and enhance Fas-mediated apoptosis.38 MEN1 is known as multiple endocrine neoplasia type 1 and regulates several pathways and processes by altering chromatin structure through the modification of histones.39 Except for P53, there was no report on the expression level of nine autoantibodies in serum from ESCC patients.