Details

Autor(en) / Beteiligte

• Wang, Xiaohong
• Gu, Haitao
• Qin, Dongze
• Yang, Liwang
• Huang, Wei
• Essandoh, Kobina
• Wang, Yigang
• Caldwell, Charles C.
• Peng, Tianqing
• Zingarelli, Basilia
• Fan, Guo-Chang

Titel

Exosomal miR-223 Contributes to Mesenchymal Stem Cell-Elicited Cardioprotection in Polymicrobial Sepsis

Ist Teil von

• Scientific reports, 2015-09, Vol.5 (1), p.13721-13721, Article 13721

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• Mesenchymal stem cells (MSCs) have been shown to elicit cardio-protective effects in sepsis. However, the underlying mechanism remains obscure. While recent studies have indicated that miR-223 is highly enriched in MSC-derived exosomes, whether exosomal miR-223 contributes to MSC-mediated cardio-protection in sepsis is unknown. In this study, loss-of-function approach was utilized and sepsis was induced by cecal ligation and puncture (CLP). We observed that injection of miR-223-KO MSCs at 1 h post-CLP did not confer protection against CLP-triggered cardiac dysfunction, apoptosis and inflammatory response. However, WT-MSCs were able to provide protection which was associated with exosome release. Next, treatment of CLP mice with exosomes released from miR-223-KO MSCs significantly exaggerated sepsis-induced injury. Conversely, WT-MSC-derived-exosomes displayed protective effects. Mechanistically, we identified that miR-223-KO exosomes contained higher levels of Sema3A and Stat3, two known targets of miR-223 (5p & 3p), than WT-exosomes. Accordingly, these exosomal proteins were transferred to cardiomyocytes, leading to increased inflammation and cell death. By contrast, WT-exosomes encased higher levels of miR-223, which could be delivered to cardiomyocytes, resulting in down-regulation of Sema3A and Stat3. These data for the first time indicate that exosomal miR-223 plays an essential role for MSC-induced cardio-protection in sepsis.