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TLR4 inhibits mesenchymal stem cell (MSC) STAT3 activation and thereby exerts deleterious effects on MSC-mediated cardioprotection

, : TLR4 inhibits mesenchymal stem cell (MSC) STAT3 activation and thereby exerts deleterious effects on MSC-mediated cardioprotection. Plos One 5(12): E14206-E14206

Bone marrow-derived mesenchymal stem cells (MSC) improve myocardial recovery after ischemia/reperfusion (I/R) injury. These effects are mediated in part by the paracrine secretion of angiogenic and tissue growth-promoting factors. Toll-like receptor 4 (TLR4) is expressed by MSC and induces apoptosis and inhibits proliferation in neuronal progenitors as well as many other cell types. It is unknown whether knock-out (KO) of TLR4 will change the paracrine properties of MSC and in turn improve MSC-associated myocardial protection. This study explored the effect of MSC TLR4 on the secretion of angiogenic factors and chemokines in vitro by using ELISA and cytokine array assays and investigated the role of TLR4 on MSC-mediated myocardial recovery after I/R injury in an isolated rat heart model. We observed that MSC isolated from TLR4 KO mice exhibited a greater degree of cardioprotection in a rat model of myocardial I/R injury. This enhanced protection was associated with increased angiogenic factor production, proliferation and differentiation. TLR4-deficiency was also associated with decreased phosphorylation of PI-3K and AKT, but increased activation of STAT3. siRNA targeting of STAT3 resulted in attenuation of the enhanced cardioprotection of TLR4-deficient MSC. This study indicates that TLR4 exerts deleterious effects on MSC-derived cardioprotection following I/R by a STAT3 inhibitory mechanism.


PMID: 21151968

DOI: 10.1371/journal.pone.0014206

Other references

Mikuz, Vasja, 2006: Polz rodu Gisortia v spodnjeeocenskih apnencih kamnoloma Griza, JZ Slovenija. In this paper a rock core of snail species Gisortia cf. murchisoni (d'Archiac) is described from the Middle Cuisian alveolinal-nummulitic limestone at the Griza quarry i the river Rizana valley. Remains of macrofauna in these limestone are ra...

Y.K.M.M.C.O, 2008: Two-stage growth of porphyroblastic biotite and garnet in the Barrovian metapelites of the Imjingang Belt, central Korea. Journal of Metamorphic Geology 26(3): 385-399

Rosengart T.K.; Kupferschmid J.P.; Casscells W.; Unger E.; Maciag T.; Clark R.E., 1987: Pharmacokinetics and distribution of endothelial cell growth factor with and without heparin in the rat. Clinical Research 35(3): 321A

Mitchell, R.J.; Marrs, R.H.; L.D.c, M.G.; Auld, M.H.D., 1997: A study of succession on lowland heaths in Dorset, southern England: Changes in vegetation and soil chemical properties. 1. Lowland heaths are high-profile ecosystems for conservation action in England, but they are under threat from invasion by Betula spp., Pinus sylvestris, Pteridium aquilinum, Rhododendron ponticum and Ulex europaeus. 2. Ten heathland sites in th...

Shea, R.A.; Summers, L.G., 1966: Visual detection of point source targets. This study presents the results of an experimental investigation of an observer's ability to detect, with the unaided eye, a target satellite in a rendezvous mission. The target was represented by a point source of light moving in a simulated...

Wingate, D.L.; Barnett, T.G.; Green, W.E., 1976: The analysis of gastrointestinal myoelectric activity. Postgraduate Medical Journal 52 Suppl 7: 157-162

Storm, T.L.; Jørgensen, F., 1983: Lingual infarction and sudden blindness due to giant cell arteritis. A 72-year-old woman suffered from giant cell arteritis (GCA) which developed into lingual infarction and monocular blindness. Temporary obscuration of vision and lingual symptoms such as increasing malaise, pain and intermittent claudication may p...

Turner, E.K., 1954: Kernicterus, with special reference to double exsanguination transfusions. Medical Journal of Australia 2(22): 860-862

Stutts, M.J.; Gatzy, J.T.; Boucher, R.C., 1988: Effects of metabolic inhibition on ion transport by dog bronchial epithelium. Mammalian bronchial epithelium absorbs Na+ under basal conditions, but Cl- secretion can be induced. We studied the effects of several modes of metabolic inhibition on the bioelectric properties and solute permeability of dog bronchial epithelium...

Gaut, Z.N.; Huggins, C.G., 1966: Effect of epinephrine on the metabolism of the inositol phosphatides in rat heart in vivo. Nature 212(5062): 612-613