ELTD1 is expressed in endothelial and vascular smooth muscle cells and has a role in angiogenesis. It has been classified as an adhesion GPCR, but as yet, no ligand has been identified and its function remains unknown. To establish its role, ELTD1 was overexpressed in endothelial cells. Expression and consequently ligand independent activation of ELTD1 results in EndMT with a loss of cell-cell contact, formation of stress fibres and mature focal adhesions and an increased expression of smooth muscle actin. The effect was pro-angiogenic, increasing Matrigel network formation and endothelial sprouting. RNA-Seq analysis after the cells had undergone EndMT revealed large increases in chemokines and cytokines involved in regulating immune response. Gene set enrichment analysis of the data identified a number of pathways involved in myofibroblast biology suggesting that the endothelial cells had undergone a type II EMT. This type of EMT is involved in wound repair and is closely associated with inflammation implicating ELTD1 in these processes.

Background. Recent studies revealed that differentiation of valvular interstitial cell into myofibroblasts played an important role in pathological valve remodeling in rheumatic valvular disease. Objective. To investigate effects of atorvastatin, olmesartan, and resveratrol on Transforming Growth Factor β1-induced fibrosis. Methods. Valvular interstitial cell was isolated from 12-weeks male New Zealand rabbit (Oryctolagus cuniculus). Culture cells was divided into 4 groups, control group, group I (0.5 mg/mL Atorvastatin), group II (100 nmol/L Olmesartan), group III (50 μM/L Resveratrol) and group IV (combinations). All group were exposed to 100 nM Transforming Growth Factor β1 for 24 hours. Results. Immunochemical staining demonstrated that cells were completely differentiated into myofibroblasts with mean expression of α-smooth muscle actin 24522.64±4566.994. Atorvastatin, olmesartan, resveratrol, and its combination significantly reduced α-smooth muscle actin expression (6823±1735.3, 6942.7±2455.9, 14176.2±3343.3, 5051.8±1612.2 respectively (p<0.001). Conclusion. Our data showed atorvastatin, olmesartan, resveratrol, and its combination significantly reduce Transforming Growth Factor β1-induced valvular fibrosis.

Introduction. Recent studies revealed that differentiation of valvular interstitial cell into myofibroblasts played an important role in pathological valve remodeling in rheumatic valvular disease. Objective. To investigate effects of atorvastatin, olmesartan, and resveratrol on Transforming Growth Factor β1-induced fibrosis. Methods. Valvular interstitial cell was isolated from 12-weeks male New Zealand rabbit (Oryctolagus cuniculus). Culture cells was divided into 4 groups, control group, group I (0.5 mg/mL Atorvastatin), group II (100 nmol/L Olmesartan), group III (50 μM/L Resveratrol) and group IV (combinations). All group were exposed to 100 nM Transforming Growth Factor β1 for 24 hours. Results. Immunochemical staining demonstrated that cells were completely differentiated into myofibroblasts with mean expression of α-smooth muscle actin 24522.64±4566.994. Atorvastatin, olmesartan, resveratrol, and its combination significantly reduced α-smooth muscle actin expression (6823±1735.3, 6942.7±2455.9, 14176.2±3343.3, 5051.8±1612.2 respectively (p<0.001). Conclusion. Our data showed atorvastatin, olmesartan, resveratrol, and its combination significantly reduce Transforming Growth Factor β1-induced valvular fibrosis.

Novel genetic and epigenetic factors involved in the development and prognosis of idiopathic pulmonary fibrosis (IPF) have been identified. We previously observed that EPB41L3 increased in the lung fibroblasts of IPF patients. Thus, we investigated the role of EPB41L3 in IPF by comparing EPB41L3 mRNA and protein expression of lung fibroblast between patients with IPF and controls. We also investigated the regulation of the epithelial-mesenchymal transition (EMT) in an epithelial cell line (A549), and the fibroblast-to-myofibroblast transition (FMT) in a fibroblast cell line (MRC5), by overexpressing and silencing EPB41L3. EPB41L3 mRNA and protein levels, as measured by RT-PCR, real-time PCR, and western blot, were significantly higher in fibroblasts derived from 14 IPF patients than in those from 10 controls. The mRNA and protein expression of EPB41L3 was upregulated during transforming growth factor-β-induced EMT and FMT. Overexpression of EPB41L3 in A549 cells using lenti-EPB41L3 transfection suppressed the mRNA and protein expression of N-cadherin and COL1A1. Treatment with EPB41L3 siRNA upregulated mRNA and protein expression of N-cadherin. Overexpression of EPB41L3 in MRC5 cells using lenti-EPB41L3 transfection suppressed mRNA and protein expression of fibronectin and α-SMA. Finally, treatment with EPB41L3 siRNA upregulated mRNA and protein expression of FN1, COL1A1, and VIM. Overall, these data strongly support an inhibitory effect of EPB41L3 on the process of fibrosis and suggest therapeutic potential of EPB41L3 as an anti-fibrotic mediator.

This study aims to explore the potential inhibition effects of staurosporine isolated from a Strepto-myces sp. SNC087 strain obtained from seawater on nasal polyps. Staurosporine possesses antimi-crobial and antihypertensive activities. This research focuses on investigating the effects of stau-rosporine on suppressing the growth and development of nasal polyps and elucidating the un-derlying mechanisms involved. The experimental design includes in vitro and ex vivo evaluations to assess the inhibition activity and therapeutic potential of staurosporine against nasal polyps. Nasal polyp-derived fibroblasts (NPDFs) were stimulated with TGF- β1 in the presence of staurosporine. The levels of -smooth muscle actin (-SMA), collagen type-I (Col-1), fibronectin, and phosphory-lated (p)-Smad 2 were investigated using western blotting. VEGF expression levels were analyzed in nasal polyp organ cultures treated with staurosporine. TGF-β1 stimulated the production of Col-1, fibronectin, and -SMA and was attenuated by staurosporine pretreatment. Furthermore, these inhibitory effects were mediated by modulation of the signaling pathway of Smad 2 in TGF-β1-induced NPDFs. Staurosporine also inhibits the production of VEGF in ex vivo NP tissues. The findings from this study will contribute to a better understanding of staurosporine’s role in nasal polyp management and provide insights into its mechanisms of action.

Cell sheet (CS) engineering using human MSC is of significant interest for regenerative medicine and this rapidly growing field translates to clinical use in a number of indications. Nevertheless, little is known of factors that define the timing of CS assembly from primary cultures which is important for planning treatments in both – autologous and allogeneic modes of use. We used a comparative in vitro approach with primary donors’ (n=14) adipose-derived MSC and evaluated the impact of healthy subject’s characteristics (age and sex), MSC culture features (population doubling time and lag-phase) and extracellular matrix (ECM) composition along with factors related to connective tissue formations (-SMA and FAP-) on CS assembly duration.