Anti-MYH2 monoclonal antibody

Our study aimed to reveal the underlying pathologic mechanisms of thyroid-associated ophthalmopathy (TAO) by integrative transcriptomics and proteomic analysis of extraocular muscles (EOM). The study involved 11 TAO patients (clinical activity score <= 2) and 11 control donors. Total RNA was extracted from EOM samples of 5 TAO patients and 5 control individuals for gene microarray analysis to reveal differentially expressed genes. Concurrently, EOM samples from 3 TAO patients and 3 control individuals were lysed for quantitative proteomic analysis. Differentially expressed genes and proteins were identified, followed by functional and pathway enrichment analysis and protein-protein interaction network construction. Concordance between proteins and transcripts was examined, and functional annotations were conducted. Expressions of versican (VCAN) and lipocalin 1 (LCN1) in EOM samples from another 3 TAO patients and 3 control individuals were measured by western blotting. In total, 952 genes and 137 proteins were identified as differentially expressed, as well as 96 differentially expressed proteins without significantly changed mRNA abundance. Proteins mainly related to the composition (such as MYH1, MYH2, and MYH13) and contraction force (MYH3, MYH8, ACTN3, and TNNT1) of the muscle fibers were significantly up-regulated in EOM samples of TAO, as well as those (such as VCAN, MPZ, and PTPRC) associated with cell adhesion. In addition, differentially expressed proteins related to the components and metabolism of extracellular matrix (ECM) (such as COL1A1, COL1A2, COL2A1, VCAN, OGN, and DCN) were identified. Similarly, expressions of genes involved in cell adhesion and ECM metabolism were significantly different between EOM samples of TAO patients and controls. Western blotting verified that VCAN involved in ECM proteoglycans and diseases associated with glycosaminoglycan metabolism was markedly higher in EOM samples of TAO, whereas LCN1 was obviously decreased. In conclusion, this study demonstrated the significantly altered cellular components of EOM, muscle contraction, cell adhesion and ECM metabolism, which might be involved in the pathologic mechanisms and/or consequences of TAO.

Background Muscle flap is a valuable option in soft tissue reconstruction. Denervated skeletal muscle is known to undergo degeneration. However, information regarding histological and genetic changes in muscle free flap without reinnervation over long-term follow-up remains unclear. Methods We collected flap muscles obtained during secondary exploration surgery after more than 15 years of previous muscle free flap without reinnervation. Compared with normal muscle and fat, histomorphometric and gene expression analysis of flap muscle were performed. Results During the study period, we collected 5 samples of previous muscle free flap. The mean SD postoperative duration after free flap was 18.6 +/- 4.0 years. All flap muscles were replaced with adipose tissue based on gross and histological findings. In flap muscle, the expression of gene related to muscle-specific MYH2 gene was downregulated, whereas the expression of genes related to adipose, fibroadipogenic progenitor, and blood vessel was upregulated compared with that of normal muscle. Vascular density and pattern were also similar to those in normal fat. Conclusions We demonstrated that muscle free flap without reinnervation eventually converts into adipose tissue regardless of spontaneous reinnervation during muscle regeneration. The long-term findings of the present study will be valuable for muscle flap selection and prognosis.