Received:20 September 2019,
Published:30 March 2020
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Xiaoxu LI, Jian HUANG, Li JIAO, et al. Effects of hypoxia on expression of formyl peptide receptor 1 in rat lung fibroblasts
Xiaoxu LI, Jian HUANG, Li JIAO, et al. Effects of hypoxia on expression of formyl peptide receptor 1 in rat lung fibroblasts
Objective
2
To study the effect of hypoxia on the expression of formyl peptide receptor 1 (FPR1) in rat lung fibroblasts.
Methods
2
We tested the chemotactic activity of 10
100
and 1 000 nmol/L FPR agonist (fMLF) for lung fibroblasts isolated from adult female SD rats using Boyden chemotaxis chamber assay. The cells were cultured in a hypoxic incubator (1% O
2
5% CO
2
and 94% N
2
) at 37 ℃ for 24 h
and the culture supernatant was collected and treated with the FPR-specific antagonist tBoc before assessing fibroblast chemotactic activity mediated by FPR. Rat lung fibroblasts cultured in a normoxic condition or in a hypoxic incubator (1% O
2
) for 2
12
and 24 h were tested for mRNA and protein levels of FPR1 and FPR agonist annexin A1 (AnxA1) using real-time PCR and Western blotting. The protein levels of FPR1 and AnxA1 were also e
xamined in cells treated with different concentrations of fMLF and in cells treated with tBoc prior to hypoxia for 24 h.
Results
2
fMLF induced obvious chemotactic migration of rat lung fibroblasts
and 100 nmol/L exhibited the strongest chemotactic activity for the fibroblasts (
P
<
0.05). The supernatant of the cells with hypoxic exposure showed a significantly higher chemotactic activity than that of the cells cultured in a normoxic condition (
P
<
0.05); the addition of tBoc significantly decreased in the chemotactic activity of the supernatants
and the reduction was more obvious with the hypoxic cell culture supernatant (
P
<
0.05). Hypoxia for 12 h significantly increased FPR1 protein expression in the lung fibroblasts (
P
<
0.05); hypoxia for 12 and 24 h significantly enhanced the protein expression of AnxA1 in the fibroblasts (
P
<
0.05). The mRNA levels of FPR1 and AnxA1 increased significantly in the lung fibroblasts after hypoxia for 2
12
and 24 h (
P
<
0.05); increasing the concentration of fMLF in the cell culture resulted in progressively increased protein levels of FPR1 and AnxA1
and their increments became significant after treatment with fMLF at 100 and 1 000 nmol/L (
P
<
0.05); this effect was significantly attenuated by the application of the FPR antagonist tBoc.
Conclusion
2
FPR1 is expressed in primary cultured rat lung fibroblasts. Hypoxia promotes the expression and secretion of FPR1 and its agonists in rat lung fibroblasts
and FPR1 activation further enhances the expression and secretion of the receptor and its agonists.
PUGLIESE S C POTH J M FINI M A The role of inflammation in hypoxic pulmonary hypertension: from cellular mechanisms to clinical phenotypes Am J Physiol Lung Cell Mol Physiol 2015 308 3 L229 L252 10.1152/ajplung.00238.2014 PUGLIESE S C, POTH J M, FINI M A, et al. The role of inflammation in hypoxic pulmonary hypertension: from cellular mechanisms to clinical phenotypes[J]. Am J Physiol Lung Cell Mol Physiol, 2015, 308(3): L229-L252. DOI: 10.1152/ajplung.00238.2014.
PUGLIESE S C KUMAR S JANSSEN W J A time- and compartment-specific activation of lung macrophages in hypoxic pulmonary hypertension J Immunol 2017 198 12 4802 4812 10.4049/jimmunol.1601692 PUGLIESE S C, KUMAR S, JANSSEN W J, et al. A time- and compartment-specific activation of lung macrophages in hypoxic pulmonary hypertension[J]. J Immunol, 2017, 198(12): 4802-4812. DOI: 10.4049/jimmunol.1601692.
LUO Y DONG H Y ZHANG B MiR-29a-3p attenuates hypoxic pulmonary hypertension by inhibiting pulmonary adventitial fibroblast activation Hypertension 2015 65 2 414 420 10.1161/HYPERTENSIONAHA.114.04600 LUO Y, DONG H Y, ZHANG B, et al. MiR-29a-3p attenuates hypoxic pulmonary hypertension by inhibiting pulmonary adventitial fibroblast activation[J]. Hypertension, 2015, 65(2): 414-420. DOI: 10.1161/HYPERTENSIONAHA.114.04600.
ZHANG N DONG M Q LUO Y Danshensu prevents hypoxic pulmonary hypertension in rats by inhibiting the proliferation of pulmonary artery smooth muscle cells via TGF-β-smad3-associated pathway Eur J Pharmacol 2018 820 1 7 10.1016/j.ejphar.2017.12.010 ZHANG N, DONG M Q, LUO Y, et al. Danshensu prevents hypoxic pulmonary hypertension in rats by inhibiting the proliferation of pulmonary artery smooth muscle cells via TGF-β-smad3-associated pathway[J]. Eur J Pharmacol, 2018, 820: 1-7. DOI:10.1016/j.ejphar.2017.12.010.
EL KASMI K C PUGLIESE S C RIDDLE S R Adventitial fibroblasts induce a distinct proinflammatory/profibrotic macrophage phenotype in pulmonary hypertension J Immunol 2014 193 2 597 609 10.4049/jimmunol.1303048 EL KASMI K C, PUGLIESE S C, RIDDLE S R, et al. Adventitial fibroblasts induce a distinct proinflammatory/profibrotic macrophage phenotype in pulmonary hypertension[J]. J Immunol, 2014, 193(2): 597-609. DOI: 10.4049/jimmunol.1303048.
WANG X LIN L J CHAI X Y Hypoxic mast cells accelerate the proliferation, collagen accumulation and phenotypic alteration of human lung fibroblasts Int J Mol Med 2020 45 1 175 185 10.3892/ijmm.2019.4400 WANG X, LIN L J, CHAI X Y, et al. Hypoxic mast cells accelerate the proliferation, collagen accumulation and phenotypic alteration of human lung fibroblasts[J]. Int J Mol Med, 2020, 45(1): 175-185. DOI: 10.3892/ijmm.2019.4400.
ZHANG L WANG H Y YANG T S Formylpeptide receptor 1 mediates the tumorigenicity of human hepatocellular carcinoma cells Oncoimmunology 2016 5 2 e1078055 10.1080/2162402X.2015.1078055 ZHANG L, WANG H Y, YANG T S, et al. Formylpeptide receptor 1 mediates the tumorigenicity of human hepatocellular carcinoma cells[J]. Oncoimmunology, 2016, 5(2): e1078055. DOI: 10.1080/2162402X.2015.1078055.
LIU M Y CHEN K Q YOSHIMURA T Formylpeptide receptors mediate rapid neutrophil mobilization to accelerate wound healing PLoS ONE 2014 9 6 e90613 10.1371/journal.pone.0090613 LIU M Y, CHEN K Q, YOSHIMURA T, et al. Formylpeptide receptors mediate rapid neutrophil mobilization to accelerate wound healing[J]. PLoS ONE, 2014, 9(6): e90613. DOI: 10.1371/journal.pone.0090613.
WANG G ZHANG L CHEN X X Formylpeptide receptors promote the migration and differentiation of rat neural stem cells Sci Rep 2016 6 25946 10.1038/srep25946 WANG G, ZHANG L, CHEN X X, et al. Formylpeptide receptors promote the migration and differentiation of rat neural stem cells[J]. Sci Rep, 2016, 6: 25946. DOI: 10.1038/srep25946.
POISSONNIER A LEGEMBRE P Boyden chamber assay to study of cell migration induced by metalloprotease cleaved-CD95L Methods Mol Biol 2017 1557 117 123 10.1007/978-1-4939-6780-3_12 POISSONNIER A, LEGEMBRE P. Boyden chamber assay to study of cell migration induced by metalloprotease cleaved-CD95L[J]. Methods Mol Biol, 2017, 1557: 117-123. DOI: 10.1007/978-1-4939-6780-3_12.
YE R D BOULAY F WANG J M International Union of Basic and Clinical Pharmacology. LXXⅢ. Nomenclature for the formyl peptide receptor (FPR) family Pharmacol Rev 2009 61 2 119 161 10.1124/pr.109.001578 YE R D, BOULAY F, WANG J M, et al. International Union of Basic and Clinical Pharmacology. LXXⅢ. Nomenclature for the formyl peptide receptor (FPR) family[J]. Pharmacol Rev, 2009, 61(2): 119-161. DOI: 10.1124/pr.109.001578.
LEE H Y JEONG Y S LEE M Intracellular formyl peptide receptor regulates na-ve CD4 T cell migration Biochem Biophys Res Commun 2018 497 1 226 232 10.1016/j.bbrc.2018.02.060 LEE H Y, JEONG Y S, LEE M, et al. Intracellular formyl peptide receptor regulates na-ve CD4 T cell migration[J]. Biochem Biophys Res Commun, 2018, 497(1): 226-232. DOI: 10.1016/j.bbrc.2018.02.060.
CHEN K Q BAO Z Y GONG W H Regulation of inflammation by members of the formyl-peptide receptor family J Autoimmun 2017 85 64 77 10.1016/j.jaut.2017.06.012 CHEN K Q, BAO Z Y, GONG W H, et al. Regulation of inflammation by members of the formyl-peptide receptor family[J]. J Autoimmun, 2017, 85: 64-77. DOI: 10.1016/j.jaut.2017.06.012.
SCHEPETKIN I A KHLEBNIKOV A I GIOVANNONI M P Development of small molecule non-peptide formyl peptide receptor (FPR) ligands and molecular modeling of their recognition Curr Med Chem 2014 21 13 1478 1504 10.2174/0929867321666131218095521 SCHEPETKIN I A, KHLEBNIKOV A I, GIOVANNONI M P, et al. Development of small molecule non-peptide formyl peptide receptor (FPR) ligands and molecular modeling of their recognition[J]. Curr Med Chem, 2014, 21(13): 1478-1504. DOI: 10.2174/0929867321666131218095521.
HARIDAS V SHETTY P SARATHKUMAR E Reciprocal regulation of pro-inflammatory Annexin A2 and anti-inflammatory Annexin A1 in the pathogenesis of rheumatoid arthritis Mol Biol Rep 2019 46 1 83 95 10.1007/s11033-018-4448-5 HARIDAS V, SHETTY P, SARATHKUMAR E, et al. Reciprocal regulation of pro-inflammatory Annexin A2 and anti-inflammatory Annexin A1 in the pathogenesis of rheumatoid arthritis[J]. Mol Biol Rep, 2019, 46(1): 83-95. DOI: 10.1007/s11033-018-4448-5.
CAI Y Q HUANG J XING H Y Contribution of FPR and TLR9 to hypoxia-induced chemoresistance of ovarian cancer cells Onco Targets Ther 2019 12 291 301 10.2147/OTT.S190118 CAI Y Q, HUANG J, XING H Y, et al. Contribution of FPR and TLR9 to hypoxia-induced chemoresistance of ovarian cancer cells[J]. Onco Targets Ther, 2019, 12: 291-301. DOI: 10.2147/OTT.S190118.
OKANO M KUMAMOTO K SAITO M Upregulated Annexin A1 promotes cellular invasion in triple-negative breast cancer Oncol Rep 2015 33 3 1064 1070 10.3892/or.2015.3720 OKANO M, KUMAMOTO K, SAITO M, et al. Upregulated Annexin A1 promotes cellular invasion in triple-negative breast cancer[J]. Oncol Rep, 2015, 33(3): 1064-1070. DOI: 10.3892/or.2015.3720.
LIAO W I WU S Y WU G C Ac2-26, an annexin A1 peptide, attenuates ischemia-reperfusion-induced acute lung injury Int J Mol Sci 2017 18 8 E1771 10.3390/ijms18081771 LIAO W I, WU S Y, WU G C, et al. Ac2-26, an annexin A1 peptide, attenuates ischemia-reperfusion-induced acute lung injury[J]. Int J Mol Sci, 2017, 18(8): E1771. DOI: 10.3390/ijms18081771.
ZOU Z ZUO D YANG J The ANXA1 released from intestinal epithelial cells alleviate DSS-induced colitis by improving NKG2A expression of Natural Killer cells Biochem Biophys Res Commun 2016 478 1 213 220 10.1016/j.bbrc.2016.07.066 ZOU Z, ZUO D, YANG J, et al. The ANXA1 released from intestinal epithelial cells alleviate DSS-induced colitis by improving NKG2A expression of Natural Killer cells[J]. Biochem Biophys Res Commun, 2016, 478(1): 213-220. DOI: 10.1016/j.bbrc.2016.07.066.
SENCHENKOVA E Y ANSARI J BECKER F Novel role for the AnxA1-Fpr2/ALX signaling Axis as a key regulator of platelet function to promote resolution of inflammation Circulation 2019 140 4 319 335 10.1161/CIRCULATIONAHA.118.039345 SENCHENKOVA E Y, ANSARI J, BECKER F, et al. Novel role for the AnxA1-Fpr2/ALX signaling Axis as a key regulator of platelet function to promote resolution of inflammation[J]. Circulation, 2019, 140(4): 319-335. DOI: 10.1161/CIRCULATIONAHA.118.039345.
刘 艳华 李 宾公 王 裕勤 敲低Runt相关转录因子3(RUNX3)抑制低氧诱导的内皮细胞间质转分化 细胞与分子免疫学杂志 2016 32 12 1627 1631 10.13423/j.cnki.cjcmi.007979 刘艳华, 李宾公, 王裕勤, 等.敲低Runt相关转录因子3(RUNX3)抑制低氧诱导的内皮细胞间质转分化[J].细胞与分子免疫学杂志, 2016, 32(12): 1627-1631. DOI: 10.13423/j.cnki.cjcmi.007979.
LIU Y H LI B G WANG Y Q Knockdown of RUNX3 inhibits hypoxia-induced endothelial-to-mesenchymal transition of human cardiac microvascular endothelial cells Chin J Cell Mol Immunol 2016 32 12 1627 1631 10.13423/j.cnki.cjcmi.007979 LIU Y H, LI B G, WANG Y Q, et al. Knockdown of RUNX3 inhibits hypoxia-induced endothelial-to-mesenchymal transition of human cardiac microvascular endothelial cells[J]. Chin J Cell Mol Immunol, 2016, 32(12): 1627-1631. DOI: 10.13423/j.cnki.cjcmi.007979.
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