Mesenchymal stem cells inhibited the apoptosis of alveolar epithelial cells caused by ARDS through CXCL12/CXCR4 axis

Abstract

Mesenchymal stem cells (MSCs) have a wide range of anti-inflammatory and immunomodulatory effects and have been observed to have potential therapeutic potential in the clinical treatment of various diseases. We pretreated lung cancer cells A549 with tumor necrosis factor (TNF-α), knocked down the key chemokine receptor CXCR4 on MSCs using lentivirus, and induced acute respiratory distress syndrome (ARDS) mouse model using lipopolysaccharide (LPS) and CXCL12 expression in vivo by adeno-associated virus (AAV-rh10) infection in mice. By co-culturing the MSCs with A549 and in vivo experiments, we observed the effects of MSCs on cell biological functions after inflammatory stimulation, oxidative stress, and the amelioration of lung injury in ARDS mice. TNF-α inhibited A549 proliferation and promoted apoptosis, scorch death-related factor activity, and oxidative stress factor were increased and CXCL12 levels in the cell supernatant were decreased. The co-culture of MSCs was able to increase cell activity and decrease oxidative stress factor levels, and this effect was not present after the knockdown of CXCR4 in MSCs. In vivo transplantation of MSCs significantly attenuated lung injury in ARDS, inhibited serum pro-inflammatory factors in mice, and down-regulated expression of apoptotic and focal factors in lung tissues while blocking CXCR4 or CXCL12 lost the repairing effect of MSCs on ARDS lung tissues. After the co-culture of MSC and lung cancer cells, the expression of CXCR4 on the surface of lung cancer cells was significantly increased, and more CXCR4 and CXCL12 acted together to activate more pro-survival pathways and inhibit apoptosis induced by TNF-α.

Astragalus polysaccharides augment BMSC homing via SDF-1/CXCR4 modulation: a novel approach to counteract peritoneal mesenchymal transformation and fibrosis

“…SDF-1 is a pivotal chemokine that plays essential roles in the maintenance, mobilization, and attraction of stem cells, with its expression notably upregulated at injury sites to draw MSCs, which express the CXCR4 receptor, to the damaged regions [38,39]. Our findings demonstrated that PDF induced an increase in SDF-1 expression in rat peritoneum, peritoneal cavity, peripheral blood, and PMCs.…”

CXCR4/CXCL12 axis: “old” pathway as “novel” target for anti‐inflammatory drug discovery

“…When CXCR4/CXCL12 axis was knocked out, the inhibitory effect of MSCs on lung injury disappeared. These findings proved that the CXCR4/CXCL12 axis mediated the repair effect of MSCs on lung tissue injury 105 …”

“…These findings proved that the CXCR4/CXCL12 axis mediated the repair effect of MSCs on lung tissue injury. 105 AMD3100 is the most commonly used CXCR4 antagonist in the studies on asthma. A natural serum albumin fragment, EPI-X4, is also a potential peptide anti-CXCR4 drug, which can bind to CXCR4 with high affinity and inhibit its activity.…”

Carnosol alleviates sepsis‐induced pulmonary endothelial barrier dysfunction by targeting nuclear factor erythroid2‐related factor 2/sirtuin‐3 signaling pathway to attenuate oxidative damage

“…After dewaxing and rehydrating with xylene and ethanol of different concentrations, the sections were processed by the following steps: staining with hematoxylin (G1120, Solarbio, China) solution for 30 s, rinsing with running water for 5 min, soaking in 1% acid alcohol for 5 s, and counterstaining with eosin Ysolution (G1120, Solarbio, China) for 2 min. Smith pathological score system was used for evaluating pathological injury of lung tissue (He et al, 2022).…”