PGE2 receptor EP3 inhibits water reabsorption and contributes to polyuria and kidney injury in a streptozotocin-induced mouse model of diabetes

Hassouneh, Ramzi; Nasrallah, Rania; Zimpelmann, Joe; Gutsol, Alex; Eckert, David; Ghossein, Jamie; Burns, Kevin D.; Hébert, Richard

doi:10.1007/s00125-016-3916-5

Cited by 32 publications

(32 citation statements)

References 50 publications

(98 reference statements)

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“…12,13 Inner medullary CD display blunted AVP-water flux but enhanced urea permeability in response to PGE2. 14,15 We have recently demonstrated a role for PGE2/EP1 in PT water transport, 16 and confirmed that a disturbance in EP3 function only partially contributes to defective urine-concentrating ability in diabetic mice, 17 highlighting a possible involvement of EP1 in kidney concentrating function. Accumulating evidence suggests that a sustained activation of the local RAS within the CD has a key role in the development of angiotensin-II-dependent hypertension.…”

mentioning

confidence: 58%

“…This is interesting considering that we showed that COX1 and COX2 were unchanged in EP3 − / − . 17 Though not much is known about the signals that trigger COX2 downregulation, Haddad et al 30 demonstrated that EP1 may promote COX2 ubiquitination and subsequent degradation. In the medulla, the data suggest that both COX1 and COX2 are downregulated by PGE2/EP1, but not as simple to interpret at this time, considering that Htn mice also display similar changes as HtnEP1 − / − with respect to COX1 mRNA expression, yet EP1 mRNA levels are significantly elevated in Htn medulla.…”

Section: Discussionmentioning

confidence: 99%

“…Glomerular filtration rate (GFR) was estimated in conscious mice by fluorescein isothiocyanate-labeled (FITC)-inulin clearance (Sigma-Aldrich, Oakville, ON, USA) as described. 17,24 Mice were injected with FITC-inulin (3.74 μl/ g BW; Sigma-Aldrich, St Louis, MO, USA) via tail vein. Blood was collected at timed intervals from the saphenous vein into heparinized capillary tubes and centrifuged.…”

Section: Glomerular Filtration Ratementioning

confidence: 99%

“…The CCD and IMCD were microdissected for in vitro microperfusion and the measurement of net fluid reabsorption (Jv) as described. 16,17 Briefly, the bath solution was exchanged at 0.5 ml/min and maintained at 37°C. For the CCD, the perfusate was hypotonic at 180 mOsm vs 290 mOsm for the bath; and the perfusate for the IMCD was isotonic at 290 mOsm vs 440 mOsm for the bath.…”

Section: In Vitro Microperfusionmentioning

confidence: 99%

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PGE2 EP1 receptor inhibits vasopressin-dependent water reabsorption and sodium transport in mouse collecting duct

Nasrallah

Zimpelmann

Eckert

et al. 2018

Laboratory Investigation

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PGE2 regulates glomerular hemodynamics, renin secretion, and tubular transport. This study examined the contribution of PGE2 EP1 receptors to sodium and water homeostasis. Male EP1-/- mice were bred with hypertensive TTRhRen mice (Htn) to evaluate blood pressure and kidney function at 8 weeks of age in four groups: wildtype (WT), EP1-/-, Htn, HtnEP1-/-. Blood pressure and water balance were unaffected by EP1 deletion. COX1 and mPGE2 synthase were increased and COX2 was decreased in mice lacking EP1, with increases in EP3 and reductions in EP2 and EP4 mRNA throughout the nephron. Microdissected proximal tubule sglt1, NHE3, and AQP1 were increased in HtnEP1-/-, but sglt2 was increased in EP1-/- mice. Thick ascending limb NKCC2 was reduced in the cortex but increased in the medulla. Inner medullary collecting duct (IMCD) AQP1 and ENaC were increased, but AVP V2 receptors and urea transporter-1 were reduced in all mice compared to WT. In WT and Htn mice, PGE2 inhibited AVP-water transport and increased calcium in the IMCD, and inhibited sodium transport in cortical collecting ducts, but not in EP1-/- or HtnEP1-/- mice. Amiloride (ENaC) and hydrochlorothiazide (pendrin inhibitor) equally attenuated the effect of PGE2 on sodium transport. Taken together, the data suggest that EP1 regulates renal aquaporins and sodium transporters, attenuates AVP-water transport and inhibits sodium transport in the mouse collecting duct, which is mediated by both ENaC and pendrin-dependent pathways.

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confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Glomerular Filtration Ratementioning

confidence: 99%

Section: In Vitro Microperfusionmentioning

confidence: 99%

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PGE2 EP1 receptor inhibits vasopressin-dependent water reabsorption and sodium transport in mouse collecting duct

Nasrallah

Zimpelmann

Eckert

et al. 2018

Laboratory Investigation

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“…It is the most widely produced prostanoid in the human body . PGE2 plays important roles in various pathological and physiological functions, such as cell proliferation, apoptosis, cancer, inflammation, hypertension, Alzeheimer's disease, diabetes and immune response . PGE2 functions through activation of four specific G‐protein‐coupled receptors (GPCR) subtypes, termed EP1, EP2, EP3 and EP4 .…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin E2 increases migration and proliferation of human glioblastoma cells by activating transient receptor potential melastatin 7 channels

Tian

Yang

et al. 2018

J Cellular Molecular Medi

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Recent studies showed that both prostaglandin E2 (PGE2) and transient receptor potential melastatin 7 (TRPM7) play important roles in migration and proliferation of human glioblastoma cells. In this study, we tested the association between PGE2 and TRPM7. We found that PGE2 increased TRPM7 currents in HEK293 and human glioblastoma A172 cells. The PGE2 EP3 receptor antagonist L‐798106 abrogated the PGE2 stimulatory effect, while EP3 agonist 17‐phenyl trinor prostaglandin E2 (17‐pt‐PGE2) mimicked the effect of PEG2 on TRPM7. The TRPM7 phosphotransferase activity‐deficient mutation, K1646R had no effect on PGE2 induced increase of TRPM7 currents. Inhibition of protein kinase A (PKA) activity by Rp‐cAMP increased TRPM7 currents. TRPM7 PKA phosphorylation site mutation S1269A abolished the PGE2 effect on TRPM7 currents. PGE2 increased both mRNA and membrane protein expression of TRPM7 in A172 cells. Knockdown of TRPM7 by shRNA abrogated the PGE2 stimulated migration and proliferation of A172 cells. Blockage of TRPM7 with 2‐aminoethoxydiphenyl borate (2‐APB) or NS8593 had a similar effect as TRPM7‐shRNA. In conclusion, our results demonstrate that PGE2 activates TRPM7 via EP3/PKA signalling pathway, and that PGE2 enhances migration and proliferation of human glioblastoma cells by up‐regulation of the TRPM7 channel.

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Melatonin improved glucose homeostasis is associated with the reprogrammed gut microbiota and reduced fecal levels of short‐chain fatty acids in db/db mice

Ban

Chi

Tan

et al. 2023

Food Science & Nutrition

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Accumulated evidence shows that melatonin possesses the potential to improve lipid metabolism by modifying gut microbiota and glucose metabolism via regulating the melatonin receptor signaling pathway. However, the contribution of melatonin consumption on glucose homeostasis by affecting gut microbiota has not been investigated in diabetes. In the current work, we investigated the effect of melatonin administration on gut microbiota and glucose homeostasis in db/db mice, a type 2 diabetes model with leptin receptor deficiency. Administration of melatonin through drinking water (at 0.25% and 0.50%) for 12 weeks decreased diabetic polydipsia and polyuria, increased insulin sensitivity and impeded glycemia. The accumulated fecal levels of total short‐chain fatty acids (SCFAs) and acetic acid are positively correlated with diabetes‐related parameters—homeostasis model assessment of insulin resistance (HOMA‐IR) index and fasting blood glucose (FBG) level. The reprogramming of gut microbiota structure and abundance and the reduction of fecal levels of SCFAs, including acetic acid, butyric acid, isovaleric acid, caproic acid, and isobutyric acid, by melatonin may be beneficial for enhancing insulin sensitivity and lowering FBG, which were verified by the results of correlation analysis between acetic acid or total SCFAs and HOMA‐IR and FBG. In addition, the melatonin downregulated hepatic genes, including fructose‐1,6‐bisphosphatase 1, forkhead box O1 alpha, thioredoxin‐interacting protein, phosphoenolpyruvate carboxy‐kinase (PEPCK), PEPCK1 and a glucose‐6‐phosphatase catalytic subunit, that responsible for gluconeogenesis support the result that melatonin improved glucose metabolism. Overall, results showed that the melatonin supplementation reduced fecal SCFAs level via reprogramming of gut microbiota, and the reduction of fecal SCFAs level is associated with improved glucose homeostasis in db/db mice.

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PGE2 receptor EP3 inhibits water reabsorption and contributes to polyuria and kidney injury in a streptozotocin-induced mouse model of diabetes

Cited by 32 publications

References 50 publications

PGE2 EP1 receptor inhibits vasopressin-dependent water reabsorption and sodium transport in mouse collecting duct

PGE2 EP1 receptor inhibits vasopressin-dependent water reabsorption and sodium transport in mouse collecting duct

Prostaglandin E2 increases migration and proliferation of human glioblastoma cells by activating transient receptor potential melastatin 7 channels

Melatonin improved glucose homeostasis is associated with the reprogrammed gut microbiota and reduced fecal levels of short‐chain fatty acids in db/db mice

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