The δ-Opioid Receptor Differentially Regulates MAPKs and Anti-inflammatory Cytokines in Rat Kidney Epithelial Cells Under Hypoxia
Hypoxic injury is one of the most important factors in progressive kidney disorders. Since we have found that δ-opioid receptor (DOR) is neuroprotective against hypoxic stress through a differential regulation of mitogen-activated protein kinases (MAPKs) and anti-inflammatory cytokines, we asked if...
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Frontiers Media S.A.
2020-01-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2019.01572/full |
| _version_ | 1818035841379860480 |
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| author | Fengbao Luo Renfang Xu Guanglai Song Hao Lu Xiaozhou He Ying Xia |
| author_facet | Fengbao Luo Renfang Xu Guanglai Song Hao Lu Xiaozhou He Ying Xia |
| author_sort | Fengbao Luo |
| collection | DOAJ |
| description | Hypoxic injury is one of the most important factors in progressive kidney disorders. Since we have found that δ-opioid receptor (DOR) is neuroprotective against hypoxic stress through a differential regulation of mitogen-activated protein kinases (MAPKs) and anti-inflammatory cytokines, we asked if DOR that is highly expressed in the kidney can modulate renal MAPKs and anti-inflammatory cytokines under hypoxia. We exposed cultured rat kidney epithelial cells (NRK-52E) to prolonged hypoxia (1% O2) with applications of specific DOR agonist or/and antagonist to examine if DOR affects hypoxia-induced changes in MAPKs and anti-inflammatory cytokines. The results showed that endogenous DOR expression remained unchanged under hypoxia, while DOR activation with UFP-512 (a specific DOR agonist) reversed the hypoxia-induced up-regulation of ERK1/2 and p38 phosphorylation. DOR inhibition with naltrindole had no appreciable effect on the hypoxia-induced changes in ERK1/2 phosphorylation, but increased p38 phosphorylation. DOR inhibition with naltrindole attenuated the effects of DOR activation on the changes in ERK1/2 and p38 phosphorylation in hypoxia. Moreover, DOR activation/inhibition differentially affected the expression of transcriptional repressor B-cell lymphoma 6 (Bcl-6), anti-inflammatory cytokines tristetraprolin (TTP), and interleukin-10 (IL-10). Taken together, our novel data suggest that DOR activation differentially regulates ERK1/2, p38, Bcl-6, TTP, and IL-10 in the renal cells under hypoxia. |
| first_indexed | 2024-12-10T07:01:28Z |
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| id | doaj.art-8b9915b1bce64517bcdb2e68a5ade439 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-10T07:01:28Z |
| publishDate | 2020-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-8b9915b1bce64517bcdb2e68a5ade4392022-12-22T01:58:18ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-01-011010.3389/fphys.2019.01572496064The δ-Opioid Receptor Differentially Regulates MAPKs and Anti-inflammatory Cytokines in Rat Kidney Epithelial Cells Under HypoxiaFengbao Luo0Renfang Xu1Guanglai Song2Hao Lu3Xiaozhou He4Ying Xia5Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, ChinaDepartment of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, ChinaDepartment of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, ChinaDepartment of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, ChinaDepartment of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, ChinaShanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Fudan University, Shanghai, ChinaHypoxic injury is one of the most important factors in progressive kidney disorders. Since we have found that δ-opioid receptor (DOR) is neuroprotective against hypoxic stress through a differential regulation of mitogen-activated protein kinases (MAPKs) and anti-inflammatory cytokines, we asked if DOR that is highly expressed in the kidney can modulate renal MAPKs and anti-inflammatory cytokines under hypoxia. We exposed cultured rat kidney epithelial cells (NRK-52E) to prolonged hypoxia (1% O2) with applications of specific DOR agonist or/and antagonist to examine if DOR affects hypoxia-induced changes in MAPKs and anti-inflammatory cytokines. The results showed that endogenous DOR expression remained unchanged under hypoxia, while DOR activation with UFP-512 (a specific DOR agonist) reversed the hypoxia-induced up-regulation of ERK1/2 and p38 phosphorylation. DOR inhibition with naltrindole had no appreciable effect on the hypoxia-induced changes in ERK1/2 phosphorylation, but increased p38 phosphorylation. DOR inhibition with naltrindole attenuated the effects of DOR activation on the changes in ERK1/2 and p38 phosphorylation in hypoxia. Moreover, DOR activation/inhibition differentially affected the expression of transcriptional repressor B-cell lymphoma 6 (Bcl-6), anti-inflammatory cytokines tristetraprolin (TTP), and interleukin-10 (IL-10). Taken together, our novel data suggest that DOR activation differentially regulates ERK1/2, p38, Bcl-6, TTP, and IL-10 in the renal cells under hypoxia.https://www.frontiersin.org/article/10.3389/fphys.2019.01572/fullkidneyNRK-52E cellhypoxiaDORMAPKsBcl-6 |
| spellingShingle | Fengbao Luo Renfang Xu Guanglai Song Hao Lu Xiaozhou He Ying Xia The δ-Opioid Receptor Differentially Regulates MAPKs and Anti-inflammatory Cytokines in Rat Kidney Epithelial Cells Under Hypoxia Frontiers in Physiology kidney NRK-52E cell hypoxia DOR MAPKs Bcl-6 |
| title | The δ-Opioid Receptor Differentially Regulates MAPKs and Anti-inflammatory Cytokines in Rat Kidney Epithelial Cells Under Hypoxia |
| title_full | The δ-Opioid Receptor Differentially Regulates MAPKs and Anti-inflammatory Cytokines in Rat Kidney Epithelial Cells Under Hypoxia |
| title_fullStr | The δ-Opioid Receptor Differentially Regulates MAPKs and Anti-inflammatory Cytokines in Rat Kidney Epithelial Cells Under Hypoxia |
| title_full_unstemmed | The δ-Opioid Receptor Differentially Regulates MAPKs and Anti-inflammatory Cytokines in Rat Kidney Epithelial Cells Under Hypoxia |
| title_short | The δ-Opioid Receptor Differentially Regulates MAPKs and Anti-inflammatory Cytokines in Rat Kidney Epithelial Cells Under Hypoxia |
| title_sort | δ opioid receptor differentially regulates mapks and anti inflammatory cytokines in rat kidney epithelial cells under hypoxia |
| topic | kidney NRK-52E cell hypoxia DOR MAPKs Bcl-6 |
| url | https://www.frontiersin.org/article/10.3389/fphys.2019.01572/full |
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