Integrated transcriptomic and metabolomic analysis reveals arginine-citrulline gene-compound network is critical for severe adhesive capsulitis progression
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ABSTRACT: Adhesive capsulitis (AC) affects 2–5% of the population worldwide. Patients with severe AC fail to regain a complete range of movement and experience years of shoulder pain. Unfortunately, the underlying mechanism of severe AC remains unclear. Here, we performed an integrated transcriptomic and metabolomic data analysis of serum and tissue samples from patients with severe AC, mild AC, and healthy controls. Pathways related to muscle development and myogenesis positively correlated with severe AC progression. Further, we identified an arginine-citrulline gene-compound network that may play a central role in severe AC. Comparing differentially regulated metabolites from tissue and serum, two phospholipids were recognized as potential serum markers for severe AC. In conclusion, this is the first comprehensive integrated -omics study on severe AC and provides insights into genes and compounds of the arginine-citrulline metabolic pathway that may be potential therapeutic targets for treating AC.
Project description:We compared genes from tissue of patients with adhesive capsulitis (AC) with those having surgery for shoulder instability to determine potential biomarkers specific to AC through transcriptomic analysis. Our results presented increased expression of PDGFB, COL18A1 and MMP9 in patients with AC, while TNFA expression was reduced.
Project description:Integrated transcriptomic and metabolomic analysis reveals arginine-citrulline gene-compound network is critical for severe adhesive capsulitis progression
Project description:This project aims to explore the pathogenesis of human frozen shoulder and screen for molecular markers. The blood and tissue samples of patients with severe and mild frozen shoulder and the control group were collected, and the integrated analysis of transcriptomics, metabolomics, and proteomics was performed on these samples.
Project description:The above study is an original research that employs transcriptomics analysis to investigate the hypothalamic responses associated with dietary L-Citrulline treatment. L-Citrulline is a non-essential amino acid that is widely gaining research interest due to its role in thermoregulation and its efficiency as an arginine/nitric oxide precursor. Therefore, this study demonstrates that dietary supplementation of L-citrulline to broilers under different housing temperatures would stimulate regulatory pathways involved with brain development and feeding behavior. We have also identified potential candidate genes that would be beneficial in fostering further research on L-citrulline-induced hypothermia.
Project description:Global genome-wide sequencing analysis of RNA prepared from Cyp1b1-/-AC and Cyp1b1+/+AC was perfomed to gain additional insight into the cellular regulatory mechanisms impacted by Cyp1b1 expression
Project description:Transcriptomic analysis of adhesive capsulitis of the shoulder
| PRJNA590709 | ENA
Project description:Multi-Omics Analysis Unveils the Arginine-Citrulline Network's Role in Augmented Protein Citrullination and Severe Adhesive Capsulitis Progression
Project description:The main pathogenesis of the frozen shoulder is thought to be the inflammation of the intra-articular synovium and subsequent fibrosis of the shoulder joint capsule. However, the molecular pathogenesis of the frozen shoulder is still unknown. A class of non-coding RNAs, microRNAs (miRNAs) contribute to various diseases including musculoskeletal diseases. MicroRNA-26a (miR-26a) has been reported to be associated with fibrosis in several organs. This study aims to reveal the role of miR-26a on fibrosis in the shoulder capsule using a frozen shoulder model in miR-26a deficient (miR-26a KO) mice. MiR-26 KO and wild type (WT) mice were investigated using a frozen shoulder model. The range of motion of the shoulder, histopathological analysis such as synovitis, and fibrosis related-genes expression in the model mice were evaluated to determine the role of miR-26a. In WT mice, both inflammatory cell infiltration and thickening of the inferior shoulder joint capsule were observed after 1 week of immobilization, and this thickening further progressed over the subsequent 6 weeks. However, the immobilized shoulder in miR-26a KO mice consistently exhibited significantly better range of motion compared with WT mice at each point, and histological changes were notably less severe. The expression of inflammation- and fibrosis-related genes was decreased in the miR-26a KO mice compared with WT mice at 1 and 6 weeks. Together, miR-26a deficiency attenuated the severity of frozen shoulder in the immobilization model mouse. The present study suggests that miR-26a has the potential to be a target miRNA for therapeutic approach to frozen shoulder.
Project description:PAD2, one of a family of PAD enzymes that convert positively charged arginine residues on target proteins to neutrally charged citrulline, has been shown to play a role in estrogen signaling through interactions with histone H3R26. The objectives of this project are to define the role of PAD2 in estrogen receptor alpha signaling, tumor progression, and tamoxifen resistance.
Project description:PAD2, one of a family of PAD enzymes that convert positively charged arginine residues on target proteins to neutrally charged citrulline, has been shown to play a role in estrogen signaling through interactions with histone H3R26. The objectives of this project are to define the role of PAD2 in estrogen receptor alpha signaling, tumor progression, and tamoxifen resistance.