Stem cells rescue cardiomyopathy induced by P. gingivalis‐LPS via miR‐181b

• Published in: Journal of cellular physiology 2018-08, Vol.233 (8), p.5869-5876
• Main Authors: Chen, Tung‐Sheng, Battsengel, Sarnai, Kuo, Chia‐Hua, Pan, Lung‐Fa, Lin, Yueh‐Min, Yao, Chun‐Hsu, Chen, Yueh‐Sheng, Lin, Feng‐Huei, Kuo, Wei‐Wen, Huang, Chih‐Yang
• Format: Article
• Language: English
• Subjects: adipose‐derived stem cells; AKT protein; Bacterial diseases; Cardiomyocytes; Cardiomyopathy; cardiovascular disease; Cell activation; Cell death; Damage; Endotoxins; Gum disease; Inflammation; Lipopolysaccharides; miR181b; Neonates; NF-κB protein; Periodontal disease; Periodontal diseases; Periodontics; Sepsis; Stem cell transplantation; Stem cells; TLR4 protein; Toll-like receptors; Transplantation
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.26386

Systemic inflammation induced by bacterial infection is one of several causative agents for cardiovascular disorders in patients with periodontal disease. Experimental results indicate that miRNAs play important roles in systemic inflammation induced by endotoxins. Further evidence states that stem cell based therapy shows potential in the treatment of inflammatory responses induced by sepsis. This study investigates if stem cells show protective effects on cardiomyocyte damage induced by porphyromonas gingivalis‐LPS (Pg‐LPS) through regulating miRNAs. H9c2 cardiomyoblasts and neonatal rat cardiomyocytes (NRCMs) were damaged using Pg‐LPS in this study. Pg‐LPS damaged H9c2 or NRCMs were then rescued using adipose‐derived stem cells (ADSC). The experimental results reveal that Pg‐LPS treatment is capable of inducing TLR4/NFκB axis activation, cell death signaling and IGF1R/PI3 K/Akt axis suppression. miR181b was downregulated in Pg‐LPS damaged H9c2/NRCMs. All markers were improved in H9c2/NRCMs cocultured with ADSC. miR181b mimic and inhibitor confirmed that miR181b plays a central role in regulating the cardio protective effect on Pg‐LPS damaged H9c2/NRCMs cocultured with ADSC. miR181b acts as potential therapeutic marker in cardiomyopathy induced by Pg‐LPS. Transplantation of adipose‐derived stem cells show potential in the treatment of cardiomyopathy induced by porphyromonas gingivalis endotoxin via regulation of miR181b. The endotoxin (LPS) of oral bacteria (Porphyromonas gingivalis) is capable of damaging cardiomyocytes by activation of TLR4/NFκB axis as well as suppression of miR 181b expression. Co‐culture of P. gingivalis LPS damaged cardiomyocytes with adipose‐derived stem cells can inactivation of TLR4/NFκB axis by regulation of miR 181b expression, leading increase of cell viability.