Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (11): 1-7.doi: 10.6040/j.issn.1671-7554.0.2021.0162

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Mechanism of miR-146a accelerating macrophage migration induced arteriosclerosis via TLR4/MyD88 pathway

YANG Jia, ZHANG Man, CHEN Kaiming, CAO Xi   

  1. Department of Cardiology, Central Hospital Affiliated to Shenyang Medical College, Shenyang 110024, Liaoning, China
  • Published:2021-11-11

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Abstract: Objective To explore the specific mechanism of microRNA-146a(miR-146a)regulating macrophage migration induced arteriosclerosis via toll-like receptor 4(TLR4)and myeloid differentiation factor88(MyD88)pathway(TLR4/MyD88). Methods RAW264.7 macrophages were divided into blank group, ox-LDL group, miR-146a mimic group, miR-146a inhibitor group, siRNA-MyD88 group, siRNA-NC group, siRNA-MyD88+miR-146a mimic group, and siRNA-MyD88+miR-146a inhibitor group. Except the blank group, the other groups were treated with 50mg/L ox-LDL. The protein expressions of TLR4, MyD88, nuclear factor kappa-B(NF-κB), and interleukin-6(IL-6)were detected with Western blotting. The mRNA expressions of miR-146a, TLR4, MyD88, NF-κB and IL-6 were detected with qPCR. The migration ability of macrophages was detected with Transwell assay. Results (1) The ox-LDL group had higher protein expressions of TLR4 and IL-6, but lower migration ability of macrophages and lower mRNA expression of TLR4 than the blank group(P<0.01). (2) The miR-146a mimic group had lower mRNA and protein expressions of TLR4, lower migration ability of macrophages, but higher mRNA expression of miR-146a than the ox-LDL group(P<0.01). The miR-146a inhibitor group had higher mRNA and protein expressions of TLR4, higher migration ability of macrophages, but lower mRNA expression of miR-146a than the ox-LDL group(all P<0.01). (3) The shRNA-MyD88 group had lower protein expressions of MyD88, NF-κB and IL-6, and lower migration ability of macrophages than the ox-LDL group(P<0.01); there was no difference in the expressions of miR-146a and TLR4(P>0.05). The shRNA-MyD88+miR-146a mimic group had higher expression of miR-146a but lower expression of TLR4 than the shRNA-MyD88 group(P<0.01). There were no significant differences in the protein expressions of MyD88, NF-κB, IL-6 and migration rate of macrophages between shRNA-MyD88 group and shRNA-MyD88 group(P>0.05). The shRNA-MyD88+miR-146a inhibitor group had lower expression of miR-146a but higher expression of TLR4 than the shRNA-MyD88 group(P<0.01). There were no significant differences in the expressions of MyD88, NF-κB, IL-6 and migration rate of macrophages(P>0.05). Conclusion miR-146a is a protective factor of atherosclerosis, which can inhibit the process of macrophage migration by regulating the secretion of inflammatory factors by antagonizing TLR4/MyD88 pathway. This can provide a new therapeutic target for the prevention and treatment of arteriosclerosis.

Key words: miR-146a, Toll-like receptor 4, Inflammatory response, Arteriosclerosis, Macrophage migration

CLC Number: 

  • R543.5
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