Dataset Information

Substance P enhances the local activation of NK₁R-expressing c-kit⁺ cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart.

ABSTRACT:

Background

Localization of neurokinin 1 receptor (NK₁R), the endogenous receptor for neuropeptide substance P (SP), has already been described for the right atrium (RA) of the heart. However, the biological role of SP/NK₁R signal pathways in the RA remains unclear. Sprague-Dawley rats were randomly divided into 4 groups (n?=?22 each); subjected to sham, ischemia/reperfusion-injury (I/R), I/R with 5 nmole/kg SP injection (SP?+?I/R), and SP?+?I/R with 1?mg/kg RP67580 injection (RP, a selective non-peptide tachykinin NK₁R antagonist) (RP/SP?+?I/R). The left anterior descending coronary artery was occluded for 40?min followed by 1?day reperfusion with SP or SP?+?RP or without either. After 1?day, both atria and ventricles as well as the heart apexes were collected.

Results

SP promoted the expression of c-Kit, GATA4, Oct4, Nanog, and Sox2 in only the RA of the SP?+?I/R rats via NK₁R activation. In agreement with these observations, NK₁R-expressing c-Kit⁺ Nkx2.5⁺GATA4⁺ cardiac progenitor cells (CPCs) in the ex vivo RA explant outgrowth assay markedly migrated out from RA^{1 day SP?+?I/R} approximately 2-fold increase more than RA^{1 day I/R}. Treatment of SP promoted proliferation, migration, cardiosphere formation, and potential to differentiate into cardiomyocytes. Using RP inhibitor, NK₁R antagonist not only inhibited cell proliferation and migration but also reduced the formation of cardiosphere and differentiation of c-Kit⁺ CPCs.

Conclusion

SP/NK₁R might play a role as a key mediator involved in the cellular response to c-Kit⁺ CPC expansion in RA of the heart within 24?h after I/R.

SUBMITTER: Jeong YM

PROVIDER: S-EPMC7285458 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Substance P enhances the local activation of NK<sub>1</sub>R-expressing c-kit<sup>+</sup> cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart.

Jeong Yun-Mi YM Cheng Xian Wu XW Lee Kyung Hye KH Lee Sora S Cho Haneul H Kim Weon W

BMC molecular and cell biology 20200609 1

<h4>Background</h4>Localization of neurokinin 1 receptor (NK<sub>1</sub>R), the endogenous receptor for neuropeptide substance P (SP), has already been described for the right atrium (RA) of the heart. However, the biological role of SP/NK<sub>1</sub>R signal pathways in the RA remains unclear. Sprague-Dawley rats were randomly divided into 4 groups (n = 22 each); subjected to sham, ischemia/reperfusion-injury (I/R), I/R with 5 nmole/kg SP injection (SP + I/R), and SP + I/R with 1 mg/kg RP67580 ...[more]

PMID: 32517655

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Project description:TIGIT expression on natural killer (NK) cells is associated with dysfunction during chronic HIV infection, but the phenotype and biological functions of these cells in the context of acute HIV-1 infection remain poorly understood. Here, 19 acutely infected HIV-1 patients traced at first, third and twelfth month, and age-matched patients with chronic HIV-1 infection were enrolled to investigate the phenotype and functions of TIGIT expression on NK cells. We found that TIGIT-expressing NK cells did not increase in frequency in the first, third and twelfth month of infection until chronic HIV-1 infection lasted over 2 years. The number of TIGIT+NK cells in acute infection was positively associated with HIV-1 viral load (r = 0.53, P = 0.0009). CD96 was significantly upregulated on NK cells after acute infection for 1 month and in chronic infection over 2 years, while CD226 was downregulated in chronic infection over 2 years. Further, at different stages of infection, CD96-CD226+ cells diminished among total NK cells, TIGIT+NK and TIGIT-NK cells, while CD96+CD226- cells expanded. Reduced CD96-CD226+ cells and elevated CD96+CD226- cells among NK cells especially TIGIT-NK cells, had opposite associations with viral load in the first month of infection, as well as CD4 T-cell counts in including the twelfth month and more than 2 years of chronic infection. In both HIV-1-infected individuals and healthy donors, TIGIT was predominantly expressed in NKG2A-NKG2C+NK cells, with a significantly higher proportion than in NKG2A+NKG2C-NK cells. Moreover, the frequencies of TIGIT+NK cells were positively associated with the frequencies of NKG2A-NKG2C+NK cells in acute infection (r = 0.62, P < 0.0001), chronic infection (r = 0.37, P = 0.023) and healthy donors (r = 0.36, P = 0.020). Enhanced early activation and coexpression of CD38 and HLA-DR in TIGIT+NK cells were detected compared to TIGIT-NK cells, both of which were inversely associated with the decrease in CD4 T-cell counts in both acute and chronic HIV-1 infection. The ability of TIGIT+NK cells to produce TNF-α, IFN-γ and CD107a degranulation substance were consistently weaker than that of TIGIT-NK cells in both acute and chronic infection. Moreover, the functionalities of TIGIT+NK cells were lower than those of TIGIT-NK cells, except for TNF-α-CD107a+IFN-γ-NK cells. These findings highlight the phenotype and functional characteristics of TIGIT-expressing NK cells which have poor capabilities in inhibiting HIV-1 replication and maintaining CD4 T-cell counts.

Dataset Information

Substance P enhances the local activation of NK₁R-expressing c-kit⁺ cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart.

Background

Results

Conclusion

Publications

Substance P enhances the local activation of NK<sub>1</sub>R-expressing c-kit<sup>+</sup> cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Substance P enhances the local activation of NK1R-expressing c-kit+ cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart.

Background

Results

Conclusion

Publications

Substance P enhances the local activation of NK<sub>1</sub>R-expressing c-kit<sup>+</sup> cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Substance P enhances the local activation of NK₁R-expressing c-kit⁺ cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart.