Secreted Factors from Adipose Tissue-derived Mesenchymal Stem Cells Suppress Oxygen/glucose Deprivation-induced Cardiomyocyte Cell Death Via Furin/PCSK-like Enzyme Activity

Overview

Journal Biochem Biophys Rep

Specialty Biochemistry

Date 2017 Sep 29

PMID 28955916

Citations 2

Authors

Yuki Tachida

Koji Suda

Hiroyuki Nagase

Kohei Shimada

Fujio Isono

Hideki Kobayashi

Affiliations

Soon will be listed here.

Abstract

Clinical application of mesenchymal stem cells (MSCs) represents a potential novel therapy for currently intractable deteriorating diseases or traumatic injuries, including myocardial infarction. However, the molecular mechanisms of the therapeutic effects have not been precisely revealed. Herein, we report that conditioned media (CM) from rat adipose tissue-derived MSCs (ASCs) protected adult cardiomyocytes from oxygen/glucose deprivation (OGD)-induced cell death. We focused on furin/PCSK protease activity in ASC-CM because many therapeutic factors of MSCs and soluble cardioprotective factors include the PCSK cleavage site. We found that recombinant furin protected cardiomyocytes from OGD-induced cell death. The ASC-CM had potent furin/PCSK protease activity and the cardioprotective effect of the CM from ASCs in the OGD-assay was abolished by an inhibitor of the furin/PCSK-like enzyme. Microarray analysis and Western blot analysis showed PCSK5A, the secreted type of PCSK5, is the most abundantly secreted PCSK among 7 PCSK family members in ASC. Finally, knockdown of PCSK5A in ASCs decreased both the furin/PCSK protease activity and cardioprotective activity in the CM. These findings indicate an involvement of furin/PCSK-type protease(s) in the anti-ischemic activity of ASCs, and suggest a new mechanism of the therapeutic effect of MSCs.

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