Effects of Mycophenolic Acid on the Proliferation and Endothelin-1 and Interleukin-6 Secretion of Rat Pulmonary Microvascular Endothelial Cells

Abstract

Objective: To investigate the effect of mycophenolic acid (MPA) on the proliferation of rat pulmonary microvascular endothelial cells (PMVECs) and on the secretion of endothelin-1 (ET-1) and interleukin-6 (IL-6) by these cells. Methods: Rat PMVECs were treated with five different final concentrations of MPA (0, 0.1, 1, 10 and 100 μM). The fetal bovine serum-induced proliferation of the PMVECs was detected using the Cell Counting Kit-8 (CCK-8). The levels of ET-1 and IL-6 secretion were assessed by radioimmunoassays. Results: At the 24 h time point, the optical density (OD) values at 450 nm for the five groups showed that there were no significant differences between the groups treated with 0 and 0.1 μM MPA (P=0.388) or between the groups treated with 10 and 100 μM MPA (P=0.292), but the OD values were significantly different between all other pairs of groups (P<0.001). At the 48 h time point, the OD values at 450 nm for the five groups showed that there was no significant difference between the groups treated with 0 and 0.1 μM MPA (P=0.094), but the OD values were significantly different between all the other groups (P<0.001). At the 72 h time point, the OD values at 450 nm for the five groups showed that there was no significant difference between the groups treated with the final concentrations of 0 and 0.1 μM MPA (P=0.931), but the OD values were significantly different between all other pairs of groups (10 μM MPA vs 100 μM MPA: P=0.037; 0 μM MPA vs 1 μM MPA: P=0.006; 1 μM MPA vs 10 μM MPA: P=0.005; all other comparisons: P<0.001). There were no significant differences in ET-1 concentration between the groups treated with 0 and 0.1 μM MPA (P=0.156) or the groups treated with 10 and 100 μM MPA (P=0.262), but there were significant differences between all other pairs of groups (P<0.001). By contrast, there were no significant differences in IL-6 concentrations between any pair of groups (P>0.05). Conclusions: MPA inhibits fetal bovine serum-induced rat PMVEC proliferation and ET-1 secretion in a dose-dependent manner.

Functional Changes in Pulmonary Arterial Endothelial Cells Associated with BMPR2 Mutations

“…Microvascular endothelial dysfunction is a prominent feature of PAH [35]. The role of pulmonary microvascular endothelial cells in the pathogenesis of PAH is crucial [36].…”

MicroRNA-497 Induces Apoptosis and Suppresses Proliferation via the Bcl-2/Bax-Caspase9-Caspase3 Pathway and Cyclin D2 Protein in HUVECs

“…The proliferation of the HUVECs was determined using a CCK-8 assay (Dojindo Molecular Technologies, Inc.) and a 5-ethynyl-2’-deoxyuridine (EdU) assay using an EdU assay kit (Ribobio, Guangzhou, China), as previously described[14, 15]. HUVECs were cultured in 96-well plates at a density of 5×10 3 cells per well and transfected with the miR-497 mimic, miR-497 inhibitor, or their respective control RNA for 48 h. For the CCK-8 assay, 10 μL of the CCK-8 reagent was added to each well for 2 hours.…”

MicroRNA-199a-5p Regulates the Proliferation of Pulmonary Microvascular Endothelial Cells in Hepatopulmonary Syndrome

“…Defining the mechanisms underlying the microvascular alterations of HPS could facilitate the development of effective medical therapies. Proliferation of pulmonary microvascular endothelial cells (PMVECs) due to imbalanced circulating factors has been considered as a critical factor contributing to microvascular alterations [6,7]. Although many signaling pathways have been demonstrated to control PMVEC proliferation, microribonucleic acids (miRs) associated with these pathways were recently identified in control of PMVEC proliferation, extensively improving our understanding of HPS pathogenesis.…”