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Expression of dual nucleotides/cysteinyl-leukotrienes receptor GPR17 in early trafficking of cardiac stromal cells after myocardial infarction.

Cosentino S, Castiglioni L, Colazzo F, Nobili E, Tremoli E, Rosa P, Abbracchio MP, Sironi L, Pesce M - J. Cell. Mol. Med. (2014)

Bottom Line: GPR17(+) cells also expressed mesenchymal marker CD44.These experiments showed a migratory function of the receptor by treatment with UDP-glucose and leukotriene LTD4, two GPR17 pharmacological agonists.These findings suggest a regulation of heart-resident mesenchymal cells and blood-borne cellular species recruitment following myocardial infarction, orchestrated by GPR17.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio di Biologia e Biochimica dell'Aterotrombosi, Centro Cardiologico Monzino, IRCCS, Milan, Italy.

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Related in: MedlinePlus

GPR17+ expression in Sca-1+ cells before and after MI. (A) Staining with SA, Sca-1 and GPR17 antibodies showed that GPR17+ interstitial cells in the normal heart express the Sca-1 marker (arrowheads). Only occasionally, cells expressing GPR17 were Sca-1−. (B) The number of GPR17+/Sca-1+ cells (arrowheads) in the border zone of the infarct and in the ischaemic areas were elevated at 24 hrs after MI. Interestingly, the cells expressing, alternatively, only one of the markers were also increased (arrowheads), suggesting a heterogeneous origin. Dashed line indicates the boundary between the ischaemic and non-ischaemic zone.
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fig02: GPR17+ expression in Sca-1+ cells before and after MI. (A) Staining with SA, Sca-1 and GPR17 antibodies showed that GPR17+ interstitial cells in the normal heart express the Sca-1 marker (arrowheads). Only occasionally, cells expressing GPR17 were Sca-1−. (B) The number of GPR17+/Sca-1+ cells (arrowheads) in the border zone of the infarct and in the ischaemic areas were elevated at 24 hrs after MI. Interestingly, the cells expressing, alternatively, only one of the markers were also increased (arrowheads), suggesting a heterogeneous origin. Dashed line indicates the boundary between the ischaemic and non-ischaemic zone.

Mentions: The presence of Adenosine receptor A2B has been recently reported in Sca-1+/CD31− cardiac cells, implying purinergic signalling in the regulation of these cells [16]. We therefore hypothesized that GPR17 may be expressed, before and after ischaemia, in stromal cells with mesenchymal characteristics [21]. To this aim, an IF analysis was performed to assess the expression of Sca-1 marker in GPR17+ cells. The results showed that before MI induction the vast majority of GPR17+ cells expressed Sca-1 (Fig. 2A). Because of their paucity, cells expressing Sca-1 in the non-ischaemic ventricular tissue could not be quantified. At 24 and 48 hrs after ischaemia, there was a dramatic increase in the number of cells expressing both markers (Fig. 2B, Fig. S2) and the appearance of GPR17+ cells, which did not express Sca-1. Irrespectively of Sca-1 expression, GPR17+ cells appeared located in groups apparently migrating just beneath the living myocardial cells. Membrane expression of GPR17 was confirmed by Z-stack reconstruction of confocal images (Fig. S3).


Expression of dual nucleotides/cysteinyl-leukotrienes receptor GPR17 in early trafficking of cardiac stromal cells after myocardial infarction.

Cosentino S, Castiglioni L, Colazzo F, Nobili E, Tremoli E, Rosa P, Abbracchio MP, Sironi L, Pesce M - J. Cell. Mol. Med. (2014)

GPR17+ expression in Sca-1+ cells before and after MI. (A) Staining with SA, Sca-1 and GPR17 antibodies showed that GPR17+ interstitial cells in the normal heart express the Sca-1 marker (arrowheads). Only occasionally, cells expressing GPR17 were Sca-1−. (B) The number of GPR17+/Sca-1+ cells (arrowheads) in the border zone of the infarct and in the ischaemic areas were elevated at 24 hrs after MI. Interestingly, the cells expressing, alternatively, only one of the markers were also increased (arrowheads), suggesting a heterogeneous origin. Dashed line indicates the boundary between the ischaemic and non-ischaemic zone.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4196654&req=5

fig02: GPR17+ expression in Sca-1+ cells before and after MI. (A) Staining with SA, Sca-1 and GPR17 antibodies showed that GPR17+ interstitial cells in the normal heart express the Sca-1 marker (arrowheads). Only occasionally, cells expressing GPR17 were Sca-1−. (B) The number of GPR17+/Sca-1+ cells (arrowheads) in the border zone of the infarct and in the ischaemic areas were elevated at 24 hrs after MI. Interestingly, the cells expressing, alternatively, only one of the markers were also increased (arrowheads), suggesting a heterogeneous origin. Dashed line indicates the boundary between the ischaemic and non-ischaemic zone.
Mentions: The presence of Adenosine receptor A2B has been recently reported in Sca-1+/CD31− cardiac cells, implying purinergic signalling in the regulation of these cells [16]. We therefore hypothesized that GPR17 may be expressed, before and after ischaemia, in stromal cells with mesenchymal characteristics [21]. To this aim, an IF analysis was performed to assess the expression of Sca-1 marker in GPR17+ cells. The results showed that before MI induction the vast majority of GPR17+ cells expressed Sca-1 (Fig. 2A). Because of their paucity, cells expressing Sca-1 in the non-ischaemic ventricular tissue could not be quantified. At 24 and 48 hrs after ischaemia, there was a dramatic increase in the number of cells expressing both markers (Fig. 2B, Fig. S2) and the appearance of GPR17+ cells, which did not express Sca-1. Irrespectively of Sca-1 expression, GPR17+ cells appeared located in groups apparently migrating just beneath the living myocardial cells. Membrane expression of GPR17 was confirmed by Z-stack reconstruction of confocal images (Fig. S3).

Bottom Line: GPR17(+) cells also expressed mesenchymal marker CD44.These experiments showed a migratory function of the receptor by treatment with UDP-glucose and leukotriene LTD4, two GPR17 pharmacological agonists.These findings suggest a regulation of heart-resident mesenchymal cells and blood-borne cellular species recruitment following myocardial infarction, orchestrated by GPR17.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio di Biologia e Biochimica dell'Aterotrombosi, Centro Cardiologico Monzino, IRCCS, Milan, Italy.

Show MeSH
Related in: MedlinePlus