Adenosine Inhibits Chemotaxis and Induces Hepatocyte-specific Genes in Bone Marrow Mesenchymal Stem Cells

Overview

Journal Hepatology

Specialty Gastroenterology

Date 2010 Jan 2

PMID 20044808

Citations 11

Authors

Mehdi Mohamadnejad

Muhammad A Sohail

Azuma Watanabe

Diane S Krause

E Scott Swenson

Wajahat Z Mehal

Affiliations

Soon will be listed here.

Abstract

Unlabelled: Bone marrow-derived mesenchymal stem cells (MSCs) have therapeutic potential in liver injury, but the signals responsible for MSC localization to sites of injury and initiation of differentiation are not known. Adenosine concentration is increased at sites of cellular injury and inflammation, and adenosine is known to signal a variety of cellular changes. We hypothesized that local elevations in the concentration of adenosine at sites of tissue injury regulate MSC homing and differentiation. Here we demonstrate that adenosine does not induce MSC chemotaxis but dramatically inhibits MSC chemotaxis in response to the chemoattractant hepatocyte growth factor (HGF). Inhibition of HGF-induced chemotaxis by adenosine requires the A2a receptor and is mediated via up-regulation of the cyclic adenosine monophosphate (AMP)/protein kinase A pathway. This results in inhibition of cytosolic calcium signaling and down-regulation of HGF-induced Rac1. Because of the important role of Rac1 in the formation of actin stress fibers, we examined the effect of adenosine on stress fiber formation and found that adenosine inhibits HGF-induced stress fiber formation. In addition, we found that adenosine induces the expression of some key endodermal and hepatocyte-specific genes in mouse and human MSCs in vitro.

Conclusion: We propose that the inhibition of MSC chemotaxis at sites of high adenosine concentration results in localization of MSCs to areas of cellular injury and death in the liver. We speculate that adenosine might initiate the process of differentiation of MSCs into hepatocyte-like cells.

Citing Articles

Mesenchymal stromal cells in hepatic fibrosis/cirrhosis: from pathogenesis to treatment.

Yang X, Li Q, Liu W, Zong C, Wei L, Shi Y Cell Mol Immunol. 2023; 20(6):583-599.

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The role of purinergic receptors in stem cell differentiation.

Kaebisch C, Schipper D, Babczyk P, Tobiasch E Comput Struct Biotechnol J. 2016; 13:75-84.

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Effects of cytokines and chemokines on migration of mesenchymal stem cells following spinal cord injury.

Li L, Yang M, Wang C, Zhao Q, Liu J, Zhan C Neural Regen Res. 2015; 7(14):1106-12.

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Activation of adenosine receptor A2A increases HSC proliferation and inhibits death and senescence by down-regulation of p53 and Rb.

Ahsan M, Mehal W Front Pharmacol. 2014; 5:69.

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Purinergic signalling in the musculoskeletal system.

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