Transgelin as a potential target in the reversibility of pulmonary arterial hypertension secondary to congenital heart disease

Abstract

BackgroundThe reversibility of pulmonary arterial hypertension (PAH) in congenital heart disease (CHD) is of great importance for the operability of CHD. Proteomics analysis found that transgelin was significantly up‐regulated in the lung tissue of CHD‐PAH patients, especially in the irreversible group. However, how exactly it participated in CHD‐PAH development is unknown.MethodsImmunohistochemical staining and Western blot were performed for further qualitative and quantitative analysis of transgelin in the lung tissues of CHD‐PAH patients. The mechanism of transgelin in CHD‐PAH development was explored in vitro. Primary human pulmonary arterial smooth muscle cells (hPASMCs) were cultured and infected with TAGLN siRNA or TAGLN lentiviral vector. Cell morphologic change (Coomassie Brilliant Blue staining), proliferation (cell count and EdU assay), apoptosis (terminal deoxyribonucleotidyl transferase mediated dUTP nick end labeling assay and Annexin‐V flow cytometry) and migration (transwell) were evaluated following the cell treatment. The mRNA and protein expression levels were detected in real‐time PCR and Western blot.ResultsIn line with the proteomic findings, transgelin was obviously expressed in PASMC of the middle pulmonary arterioles, especially in the irreversible PAH group. Also, transgelin expression showed positive relation with pathological grading. Experiment in vitro demonstrated that transgelin overexpression promoted PASMC proliferation and migration, strengthened cytoskeleton and was accompanied by increased expression of synthetic phenotype markers (osteopontin, proliferating cell nuclear antigen) and anti‐apoptotic protein (bcl‐2). On the other hand, suppression of transgelin expression activated PASMC apoptosis, reducing cell proliferation and migration.ConclusionsTransgelin may be a potential target in the development of irreversible CHD‐PAH through inducing PASMC phenotype change, proliferation, migration and reducing cell apoptosis.

Transgelin Inhibits the Malignant Progression of Esophageal Squamous Cell Carcinomas by Regulating Epithelial–Mesenchymal Transition

“…Transgelin is a 22 kDa protein that is widely found in smooth muscle tissues ( 15 ). Transgelin is an actin gelatin that is sensitive to changes in transformation, mutation, and shape ( 16 ). However, few studies have investigated its function.…”

Myocardial proteomic profile in pulmonary arterial hypertension

“…Other promising proteins include profilin 1, which overexpression is sufficient to induce cardiomyocyte hypertrophy and sarcomere remodeling, and silencing attenuates the hypertrophic response 45 . Furthermore, 14-3-3 protein, having an anti-apoptotic role through phosphorylation-dependent binding 46 and transgelin-2, that is an actin‐binding protein implicated in actin dynamics which induce cell proliferation and migration 47 are worthy of our attention. Also, we have observed increased abundance of calreticulin, that is an effective inducer of cardiac growth, which activation might be involved in hypoxic signaling leading to pulmonary hypertension; calreticulin activity may be inhibited by cyclosporin A, thus preventing RV hypertrophy 48 .…”

Transgelins: Cytoskeletal Associated Proteins Implicated in the Metastasis of Colorectal Cancer

“…Transgelins are a family of proteins that were discovered decades ago ( Lees-Miller et al, 1987 ; Shapland et al, 1993 ). They are involved in many diseases, including asthma, hypertension, diabetes and cancer, but the role of transgelins in cancer is not very clear ( Huang et al, 2018 ; Sun et al, 2018 ; Varberg et al, 2018 ; Yin et al, 2018 ). Recently, studies have shown that transgelins are associated with CRC metastasis.…”