Suxiao Jiuxin pill promotes exosome secretion from mouse cardiac mesenchymal stem cells in vitro

Xiao Fen Ruan, Cheng Wei Ju, Yan Shen, Yutao Liu, Il-man Kim, Hong Yu, Neal Lee Weintraub, Xiao Long Wang, Yao Liang Tang

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Cardiac mesenchymal stem cells (C-MSCs) are endogenous cardiac stromal cells that play a role in heart repair after injury. C-MSC-derived exosomes (Exo) have shown protective effects against apoptosis induced by acute myocardial ischemia/reperfusion. Suxiao Jiuxin pill (SJP) is a traditional Chinese medicine (TCM) formula used in China for the treatment of acute myocardial ischemia, which contains tetramethylpyrazine (TMP) and borneol (BOR) as major components. In this study, we investigated whether SJP treatment affected exosome release from C-MSCs in vitro. C-MSCs prepared from mice were treated with SJP (62.5 μg/mL), TMP (25 μg/mL) or BOR (15 μg/mL). Using an acetylcholinesterase activity assay, we found that both SJP and TMP treatment significantly increased exosome secretion compared to the control ethanol treatment. The neutral sphingomyelinase 2 (nSMase2) pathway was important in exosome formation and packaging. But neither the level of nSMase2 mRNA nor the level of protein changed following SJP, TMP or BOR treatment, suggesting that SJP stimulated exosome release via an nSMase2-independent pathway. The Rab27a and Rab27b GTPases controlled different steps of the exosome secretion pathway. We showed that SJP treatment significantly increased the protein levels of Rab27a, SYTL4 (Rab27a effector) and Rab27b compared with the control treatment. SJP treatment also significantly upregulated the mRNA level of Rab27b, rather than Rab27a. Moreover, SJP-induced increase of C-MSC-exosome release was inhibited by Rab27b knockdown, suggesting that SJP promotes exosome secretion from C-MSCs via a GTPase-dependent pathway. This study reveals a novel mechanism for SJP in modulating cardiac homeostasis.

Original languageEnglish (US)
Pages (from-to)569-578
Number of pages10
JournalActa Pharmacologica Sinica
Volume39
Issue number4
DOIs
StatePublished - Apr 1 2018

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Exosomes
Mesenchymal Stromal Cells
Sphingomyelin Phosphodiesterase
GTP Phosphohydrolases
Therapeutics
Myocardial Ischemia
Myocardial Reperfusion
Messenger RNA
In Vitro Techniques
Secretory Pathway
Chinese Traditional Medicine
Product Packaging
Acetylcholinesterase
Stromal Cells
China
Proteins
Homeostasis
Ethanol
Apoptosis
tetramethylpyrazine

Keywords

  • GTPase
  • Rab27
  • Suxiao Jiuxin pill
  • acute myocardial ischemia
  • borneol
  • cardiac mesenchymal stem cells
  • exosomes
  • nSMase2
  • tetramethylpyrazine
  • traditional Chinese Medicine

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Suxiao Jiuxin pill promotes exosome secretion from mouse cardiac mesenchymal stem cells in vitro. / Ruan, Xiao Fen; Ju, Cheng Wei; Shen, Yan; Liu, Yutao; Kim, Il-man; Yu, Hong; Weintraub, Neal Lee; Wang, Xiao Long; Tang, Yao Liang.

In: Acta Pharmacologica Sinica, Vol. 39, No. 4, 01.04.2018, p. 569-578.

Research output: Contribution to journalArticle

Ruan, Xiao Fen ; Ju, Cheng Wei ; Shen, Yan ; Liu, Yutao ; Kim, Il-man ; Yu, Hong ; Weintraub, Neal Lee ; Wang, Xiao Long ; Tang, Yao Liang. / Suxiao Jiuxin pill promotes exosome secretion from mouse cardiac mesenchymal stem cells in vitro. In: Acta Pharmacologica Sinica. 2018 ; Vol. 39, No. 4. pp. 569-578.
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AU - Weintraub, Neal Lee

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