Endostatin Stimulates Proliferation and Migration of Myofibroblasts Isolated from Myocardial Infarction Model Rats

Abstract

Myofibroblasts contribute to the healing of infarcted areas after myocardial infarction through proliferation, migration, and production of extracellular matrix (ECM). Expression of endostatin, a cleaved fragment of type XVIII collagen, increases in the heart tissue of an experimental myocardial infarction model. In the present study, we examined the effect of endostatin on the function of myofibroblasts derived from an infarcted area. The myocardial infarction model was created by ligating the left anterior descending artery in rats. Two weeks after the operation, α-smooth muscle actin (α-SMA)-positive myofibroblasts were isolated from the infarcted area. Endostatin significantly increased the proliferation and migration of myofibroblasts in vitro. On the other hand, endostatin had no effect on the production of type I collagen, a major ECM protein produced by myofibroblasts. Endostatin activated Akt and extracellular signal-regulated kinase (ERK), and the pharmacological inhibition of these signaling pathways suppressed the endostatin-induced proliferation and migration. A knockdown of the COL18A1 gene in the myocardial infarction model rats using small interference RNA (siRNA) worsened the cardiac function concomitant with wall thinning and decreased the α-SMA-positive myofibroblasts and scar formation compared with that of control siRNA-injected rats. In summary, we demonstrated for the first time that endostatin might be an important factor in the healing process after myocardial infarction through the activation of myofibroblasts.

Small extracellular vesicles from rat plasma promote migration and proliferation of vascular smooth muscle cells

“…We examined the migration of RASM by a boyden chamber assay [36,43]. Briefly, the polycarbonate membranes with an 8 µm pore size (Costar, Cambridge, MA, USA) were coated by 2% gelatin (FUJIFILM Wako Pure Chemical) in ddH 2 O (37°C, 30 min).…”

“…We examined the proliferation of RASM with a BrdU incorporation assay kit (Exalpha Biologicals, Shirley, MA, USA) as described previously [36,43]. Briefly, RASM (4.0 × 10 3 cells/well) were seeded on a 96-well culture plate and treated for 48 hr with WsEV, SsEV (0.1, 0.3, 1.0 × 10 8 particles/ml) or PBS (Cont).…”

Polysaccharide Extracted from Bletilla striata Promotes Proliferation and Migration of Human Tenocytes

“…A review paper demonstrated the effect of ERK1/2 on cell migration through its interaction with different proteins (such as Vinexin β and Calpain 2) [53]. In 2018, a report confirmed via pharmacologically inhibiting the ERK1/2 pathway that endostatin can increase myofibroblast migration through activation of the pathway [44]. In this study, we inferred that BSP could induce HT migration through activation of the ERK1/2 pathway.…”

“…Results are shown in Figure 6E; PD98059 inhibited BSP-induced proliferation of HTs by 47% compared with BSP group and wortmannin inhibited it by 60%, while co-treatment of both inhibitors inhibited BSP-induced proliferation of HTs by 32%. To confirm the pathway based on Figure 5, we selected PD98059 (PD), one of the MEK/ERK1/2 pathway inhibitors, and wortmannin (Wort), a PI3K/Akt pathway inhibitor, for the cell pathway inhibition experiment [42][43][44]. HTs were treated with two different concentrations of PD98059 (10 and 50 µM) and wortmannin (0.5 and 1 µM) for 1 h and stimulated with 100 µg/mL BSP for 24 h. As shown in Figure 6, PD98059 significantly inhibited the MEK/ERK1/2 pathway at 10 µM (p < 0.01) with maximum inhibition at 50 µM ( Figure 6A,B).…”

Cathepsin S degrades arresten and canstatin in infarcted area after myocardial infarction in rats

“…A permanent ligation of left anterior descending coronary artery was performed to make myocardial infarction model rats as described previously [27]. The rats were anesthetized with isoflurane [flow rate: 2 l /min, concentration: 5% (induction), 2.5% (maintenance)] through endotracheal tube connected to a vaporizer (respiratory rate: 100 times/min, tidal volume: 5 m l ).…”