Tumor necrosis factor-alpha induces renal cyclooxygenase-2 expression in response to hypercalcemia

Battula, Sailaja; Hao, Shoujin; Pedraza, Paulina L.; Stier, Charles T.; Ferreri, Nicholas R.

doi:10.1016/j.prostaglandins.2012.07.001

Cited by 5 publications

(7 citation statements)

References 33 publications

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“…The data in the present study are consistent with such a model and provide another level of regulation by limiting the extent of COX-2-derived PGE 2 synthesis, via EP 3 receptor activation, thereby limiting the extent of water and NaCl excretion (7,9,22). It is well established that COX-2 expression along the TAL segment and PGE 2 production by mTAL cells can be induced by diverse stimuli (1,2,10,35,38). Indeed, PGE 2 inhibits the expression and activity of bumetanide/furosemidesensitive Na ϩ -K ϩ -Cl Ϫ cotransporter 2 (9,22), which contributes importantly to NaCl reabsorption by the TAL.…”

Section: Discussionsupporting

confidence: 87%

PGE₂EP₃receptor downregulates COX-2 expression in the medullary thick ascending limb induced by hypertonic NaCl

Hao

Hernández

Quiroz-Munoz

et al. 2014

American Journal of Physiology-Renal Physiology

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We tested the hypothesis that inhibition of EP3 receptors enhances cyclooxygenase (COX)-2 expression in the thick ascending limb (TAL) induced by hypertonic stimuli. COX-2 protein expression in the outer medulla increased approximately twofold in mice given free access to 1% NaCl in the drinking water for 3 days. The increase was associated with an approximate threefold elevation in COX-2 mRNA accumulation and an increase in PGE2 production by isolated medullary (m)TAL tubules from 77.3 ± 8.4 to 165.7 ± 10.8 pg/mg protein. Moreover, administration of NS-398 abolished the increase in PGE2 production induced by 1% NaCl. EP3 receptor mRNA levels also increased approximately twofold in the outer medulla of mice that ingested 1% NaCl. The selective EP3 receptor antagonist L-798106 increased COX-2 mRNA by twofold in mTAL tubules, and the elevation in COX-2 protein induced by 1% NaCl increased an additional 50% in mice given L-798106. COX-2 mRNA in primary mTAL cells increased twofold in response to media made hypertonic by the addition of NaCl (400 mosmol/kg H2O). L-798106 increased COX-2 mRNA twofold in isotonic media and fourfold in cells exposed to 400 mosmol/kg H2O. PGE2 production by mTAL cells increased from 79.3 ± 4.6 to 286.7 ± 6.3 pg/mg protein after challenge with 400 mosmol/kg H2O and was inhibited in cells transiently transfected with a lentivirus short hairpin RNA construct targeting exon 5 of COX-2 to silence COX-2. Collectively, the data suggest that local hypertonicity in the mTAL is associated with an increase in COX-2 expression concomitant with elevated EP3 receptor expression, which limits COX-2 activity in this segment of the nephron.

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Section: Discussionsupporting

confidence: 87%

PGE₂EP₃receptor downregulates COX-2 expression in the medullary thick ascending limb induced by hypertonic NaCl

Hao

Hernández

Quiroz-Munoz

et al. 2014

American Journal of Physiology-Renal Physiology

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“…Although the mechanisms underlying the TNFα-mediated phenotypic conversion of VSMCs remain unclear, recent evidence supports the role of COX2 induction during vascular remodeling. TNFα can induce the expression of COX2 in various cell types 18–22 , and likewise, we found that TNFα stimulates the promoter activity of COX2 and thereby enhances COX2 expression in contractile VSMCs (Fig. 2a–c).…”

Section: Discussionsupporting

confidence: 69%

“…It has also been reported that TNFα can induce the expression of cyclooxygenase-2 (COX2) in a variety of cell types, such as renal outer medulla cells, dorsal root ganglion cells, carcinoma cells, endometrial cells, and chondrocytes 18–22 , and that the induction of COX2 by TNFα plays a key role in VSMC proliferation 23 . COX regulates the rate-limiting step of the production of thromboxane A 2 (TXA 2 ) and prostaglandins, such as prostaglandin D 2 (PGD 2 ), prostaglandin I 2 (PGI 2 ), prostaglandin E 2 (PGE 2 ), and prostaglandin F 2α (PGF 2α ) 24 .…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin D2 stimulates phenotypic changes in vascular smooth muscle cells

Lee

Yun

et al. 2019

Exp Mol Med

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Since chronic inflammation is associated with the pathogenesis of atherosclerosis, inflammatory cytokines might contribute to the phenotypic modulation of vascular smooth muscle cells (VSMCs). Tumor necrosis factor α (TNFα) facilitated the transformation of contractile VSMCs to the synthetic phenotype, as determined by the expression of marker proteins and a collagen gel contraction assay. Western blot analysis and a cyclooxygenase-2 (COX2) promoter assay revealed that TNFα stimulation resulted in the induction of COX2. The overexpression, silencing, or pharmacological inhibition of COX2 significantly affected TNFα-induced phenotypic conversion, and of the tested prostaglandins, only PGD 2 significantly induced phenotypic conversion. ERK was significantly activated by PGD 2 stimulation, and the pharmacological inhibition of ERK blocked the PGD 2-induced phenotypic conversion of VSMCs. However, antagonists or agonists of PGD 2 receptors did not affect VSMC conversion. In contrast, spontaneously dehydrated forms of PGD 2 , such as PGJ 2 , Δ 12-PGJ 2 , and 15-d-PGJ 2 , strongly induced phenotypic conversion. A reporter gene assay showed that TNFα, PGD 2 , and 15-d-PGJ 2 significantly activated the peroxisome proliferator-responsive element (PPRE) promoter. In addition, the overexpression or silencing of peroxisome proliferator-activated receptor δ (PPARδ) significantly influenced 15-d-PGJ 2-induced phenotypic conversion. Finally, atherosclerotic neointima formation was significantly suppressed in mice lacking TNFα. In addition, mice fed celecoxib exhibited complete inhibition of carotid artery ligation-induced neointima formation. This study shows that PGD 2 regulates the phenotypic conversion of VSMCs by generating an endogenous ligand of PPAR, and that this leads to neointima formation in occlusive arterial disease.

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“…Furthermore, amiloride‐sensitive sodium transport was normalized after treatment by macitentan. This is in agreement with previous studies using genetically modified animals or pharmacological tools to show the inhibitory role of ET‐1 on ENaC activity (Bugaj et al ., , ). Moreover, given the lack of difference in ENaC expression between control and DHT‐treated mice, the activated ET system probably controls ENaC activity at a post‐transcriptional level.…”

Section: Discussionmentioning

confidence: 99%

“…; DiBona, ; Battula et al . ). At present, the molecular mechanism underlying the disturbance in water and sodium transport accompanying hypercalcaemia is not well understood.…”

Section: Introductionmentioning

confidence: 97%

Endothelin‐1 mediates natriuresis but not polyuria during vitamin D‐induced acute hypercalcaemia

Tokonami

Cheval

Monnay

et al. 2017

The Journal of Physiology

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Acute hypercalcaemia increases urinary sodium and water excretion; however, the underlying molecular mechanism remains unclear. Because vitamin D-induced hypercalcaemia increases the renal expression of endothelin (ET)-1, we hypothesized that ET-1 mediates the effects of hypercalcaemia on renal sodium and water handling. Hypercalcaemia was induced in 8-week-old, parathyroid hormone-supplemented, male mice by oral administration of dihydrotachysterol (DHT) for 3 days. DHT-treated mice became hypercalcaemic and displayed increased urinary water and sodium excretion compared to controls. mRNA levels of ET-1 and the transcription factors CCAAT-enhancer binding protein β and δ were specifically increased in the distal convoluted tubule and downstream segments in DHT-treated mice. To examine the role of the ET system in hypercalcaemia-induced natriuresis and polyuria, mice were treated with the ET-1 receptor antagonist macitentan, with or without DHT. Mice treated with both macitentan and DHT displayed hypercalcaemia and polyuria similar to that in mice treated with DHT alone; however, no increase in urinary sodium excretion was observed. To identify the affected sodium transport mechanism, we assessed the response to various diuretics in control and DHT-treated hypercalcaemic mice. Amiloride, an inhibitor of the epithelial sodium channel (ENaC), increased sodium excretion to a lesser extent in DHT-treated mice compared to control mice. Mice treated with either macitentan+DHT or macitentan alone had a similar response to amiloride. In summary, vitamin D-induced hypercalcaemia increases the renal production of ET-1 and decreases ENaC activity, which is probably responsible for the rise in urinary sodium excretion but not for polyuria.

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Tumor necrosis factor-alpha induces renal cyclooxygenase-2 expression in response to hypercalcemia

Cited by 5 publications

References 33 publications

PGE₂EP₃receptor downregulates COX-2 expression in the medullary thick ascending limb induced by hypertonic NaCl

PGE₂EP₃receptor downregulates COX-2 expression in the medullary thick ascending limb induced by hypertonic NaCl

Prostaglandin D2 stimulates phenotypic changes in vascular smooth muscle cells

Endothelin‐1 mediates natriuresis but not polyuria during vitamin D‐induced acute hypercalcaemia

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Tumor necrosis factor-alpha induces renal cyclooxygenase-2 expression in response to hypercalcemia

Cited by 5 publications

References 33 publications

PGE2EP3receptor downregulates COX-2 expression in the medullary thick ascending limb induced by hypertonic NaCl

PGE2EP3receptor downregulates COX-2 expression in the medullary thick ascending limb induced by hypertonic NaCl

Prostaglandin D2 stimulates phenotypic changes in vascular smooth muscle cells

Endothelin‐1 mediates natriuresis but not polyuria during vitamin D‐induced acute hypercalcaemia

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PGE₂EP₃receptor downregulates COX-2 expression in the medullary thick ascending limb induced by hypertonic NaCl

PGE₂EP₃receptor downregulates COX-2 expression in the medullary thick ascending limb induced by hypertonic NaCl