-
Journal of the Chinese Medical... Feb 2018Wound healing is an important physiological process to maintain the integrity of skin after trauma, either by accident or by intent procedure. The normal wound healing... (Review)
Review
Wound healing is an important physiological process to maintain the integrity of skin after trauma, either by accident or by intent procedure. The normal wound healing involves three successive but overlapping phases, including hemostasis/inflammatory phase, proliferative phase, and remodeling phase. Aberration of wound healing, such as excessive wound healing (hypertrophic scar and keloid) or chronic wound (ulcer) impairs the normal physical function. A large number of sophisticated experimental studies have provided insights into wound healing. This article highlights the information after 2010, and the main text includes (i) wound healing; (ii) wound healing in fetus and adult; (iii) prostaglandins and wound healing; (iv) the pathogenesis of excessive wound healing; (v) the epidemiology of excessive wound healing; (vi) in vitro and in vivo studies for excessive wound healing; (vii) stem cell therapy for excessive wound healing; and (viii) the prevention strategy for excessive wound healing.
Topics: Adult; Animals; Humans; MicroRNAs; Prostaglandin Antagonists; Prostaglandins; Stem Cell Transplantation; Transforming Growth Factor beta; Wound Healing
PubMed: 29169897
DOI: 10.1016/j.jcma.2017.11.002 -
The Cochrane Database of Systematic... Apr 2023Patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in preterm infants. Several non-pharmacological, pharmacological, and surgical... (Review)
Review
BACKGROUND
Patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in preterm infants. Several non-pharmacological, pharmacological, and surgical approaches have been explored to prevent or treat a PDA.
OBJECTIVES
To summarise Cochrane Neonatal evidence on interventions (pharmacological or surgical) for the prevention of PDA and related complications, and interventions for the management of asymptomatic and symptomatic PDA in preterm infants.
METHODS
We searched the Cochrane Database of Systematic Reviews on 20 October 2022 for ongoing and published Cochrane Reviews on the prevention and treatment of PDA in preterm (< 37 weeks' gestation) or low birthweight (< 2500 g) infants. We included all published Cochrane Reviews assessing the following categories of interventions: pharmacological therapy using prostaglandin inhibitor drugs (indomethacin, ibuprofen, and acetaminophen), adjunctive pharmacological interventions, invasive PDA closure procedures, and non-pharmacological interventions. Two overview authors independently checked the eligibility of the reviews retrieved by the search, and extracted data from the included reviews using a predefined data extraction form. Any disagreements were resolved by discussion with a third overview author. Two overview authors independently assessed the methodological quality of the included reviews using the AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews) tool. We reported the GRADE certainty of evidence as assessed by the respective review authors using summary of findings tables.
MAIN RESULTS
We included 16 Cochrane Reviews, corresponding to 138 randomised clinical trials (RCT) and 11,856 preterm infants, on the prevention and treatment of PDA in preterm infants. One of the 16 reviews had no included studies, and therefore, did not contribute to the results. Six reviews reported on prophylactic interventions for the prevention of PDA and included pharmacological prophylaxis with prostaglandin inhibitor drugs, prophylactic surgical PDA ligation, and non-pharmacologic interventions (chest shielding during phototherapy and restriction of fluid intake); one review reported on the use of indomethacin for the management of asymptomatic PDA; nine reviews reported on interventions for the management of symptomatic PDA, and included pharmacotherapy with prostaglandin inhibitor drugs in various routes and dosages, surgical PDA ligation, and adjunct therapies (use of furosemide and dopamine in conjunction with indomethacin). The quality of reviews varied. Two reviews were assessed to be high quality, seven reviews were of moderate quality, five of low quality, while two reviews were deemed to be of critically low quality. For prevention of PDA, prophylactic indomethacin reduces severe intraventricular haemorrhage (IVH; relative risk (RR) 0.66, 95% confidence interval (CI) 0.53 to 0.82; 14 RCTs, 2588 infants), and the need for invasive PDA closure (RR 0.51, 95% CI 0.37 to 0.71; 8 RCTs, 1791 infants), but it does not appear to affect the composite outcome of death or moderate/severe neurodevelopmental disability (RR 1.02, 95% CI 0.90 to 1.15; 3 RCTs, 1491 infants). Prophylactic ibuprofen probably marginally reduces severe IVH (RR 0.67, 95% CI 0.45 to 1.00; 7 RCTs, 925 infants; moderate-certainty evidence), and the need for invasive PDA closure (RR 0.46, 95% CI 0.22 to 0.96; 7 RCTs, 925 infants; moderate-certainty evidence). The evidence is very uncertain on the effect of prophylactic acetaminophen on severe IVH (RR 1.09, 95% CI 0.07 to 16.39; 1 RCT, 48 infants). Necrotising enterocolitis (NEC) was lower with both prophylactic surgical ligation (RR 0.25, 95% CI 0.08 to 0.83; 1 RCT, 84 infants), and fluid restriction (RR 0.43, 95% CI 0.21 to 0.87; 4 RCTs, 526 infants). For treatment of asymptomatic PDA, indomethacin appears to reduce the development of symptomatic PDA post-treatment (RR 0.36, 95% CI 0.19 to 0.68; 3 RCTs, 97 infants; quality of source review: critically low). For treatment of symptomatic PDA, all available prostaglandin inhibitor drugs appear to be more effective in closing a PDA than placebo or no treatment (indomethacin: RR 0.30, 95% CI 0.23 to 0.38; 10 RCTs, 654 infants; high-certainty evidence; ibuprofen: RR 0.62, 95% CI 0.44 to 0.86; 2 RCTs, 206 infants; moderate-certainty evidence; early administration of acetaminophen: RR 0.35, 95% CI 0.23 to 0.53; 2 RCTs, 127 infants; low-certainty evidence). Oral ibuprofen appears to be more effective in PDA closure than intravenous (IV) ibuprofen (RR 0.38, 95% CI 0.26 to 0.56; 5 RCTs, 406 infants; moderate-certainty evidence). High-dose ibuprofen appears to be more effective in PDA closure than standard-dose ibuprofen (RR 0.37, 95% CI 0.22 to 0.61; 3 RCTs, 190 infants; moderate-certainty evidence). With respect to adverse outcomes, compared to indomethacin administration, NEC appears to be lower with ibuprofen (any route; RR 0.68, 95% CI 0.49 to 0.94; 18 RCTs, 1292 infants; moderate-certainty evidence), oral ibuprofen (RR 0.41, 95% CI 0.23 to 0.73; 7 RCTs, 249 infants; low-certainty evidence), and with acetaminophen (RR 0.42, 95% CI 0.19 to 0.96; 4 RCTs, 384 infants; low-certainty evidence). However, NEC appears to be increased with a prolonged course of indomethacin versus a shorter course (RR 1.87, 95% CI 1.07 to 3.27; 4 RCTs, 310 infants).
AUTHORS' CONCLUSIONS
This overview summarised the evidence from 16 Cochrane Reviews of RCTs regarding the effects of interventions for the prevention and treatment of PDA in preterm infants. Prophylactic indomethacin reduces severe IVH, but does not appear to affect the composite outcome of death or moderate/severe neurodevelopmental disability. Prophylactic ibuprofen probably marginally reduces severe IVH (moderate-certainty evidence), while the evidence is very uncertain on the effect of prophylactic acetaminophen on severe IVH. All available prostaglandin inhibitor drugs appear to be effective in symptomatic PDA closure compared to no treatment (high-certainty evidence for indomethacin; moderate-certainty evidence for ibuprofen; low-certainty evidence for early administration of acetaminophen). Oral ibuprofen appears to be more effective in PDA closure than IV ibuprofen (moderate-certainty evidence). High dose ibuprofen appears to be more effective in PDA closure than standard-dose ibuprofen (moderate-certainty evidence). There are currently two ongoing reviews, one on fluid restriction for symptomatic PDA, and the other on invasive management of PDA in preterm infants.
Topics: Infant, Newborn; Humans; Ductus Arteriosus, Patent; Ibuprofen; Cyclooxygenase Inhibitors; Acetaminophen; Prostaglandin Antagonists; Systematic Reviews as Topic; Infant, Premature; Indomethacin
PubMed: 37039501
DOI: 10.1002/14651858.CD013588.pub2 -
International Journal of Clinical... Sep 2009To summarise the metabolic responses to niacin that can lead to flushing and to critically evaluate flushing mitigation research. (Review)
Review
AIMS
To summarise the metabolic responses to niacin that can lead to flushing and to critically evaluate flushing mitigation research.
METHODS AND RESULTS
This comprehensive review of the mechanism of action of niacin-induced flushing critically evaluates research regarding flushing mitigating formulations and agents. Niacin induces flushing through dermal Langerhans cells where the activation of G protein-coupled receptor 109A (GPR109A) increases arachidonic acid and prostaglandins, such as prostaglandin D(2) (PGD(2)) and prostaglandin E(2) (PGE(2)), subsequently activating prostaglandin D(2) receptor (DP(1)), prostaglandin E(2) receptor (EP(2)) and prostaglandin E receptor 4 (EP(4)) in capillaries and causing cutaneous vasodilatation. Controlling niacin absorption rates, inhibiting prostaglandin production, or blocking DP(1), EP(2) and EP(4) receptors can inhibit flushing. Niacin extended-release (NER) formulations have reduced flushing incidence, duration and severity relative to crystalline immediate-release niacin with similar lipid efficacy. Non-steroidal anti-inflammatory drugs (NSAIDs), notably aspirin given 30 min before NER at bedtime, further reduce flushing. An antagonist to the DP(1) receptor (laropiprant) combined with an ER niacin formulation can reduce flushing; however, significant residual flushing occurs with clinically-relevant dosages.
CONCLUSIONS
Niacin is an attractive option for treating dyslipidemic patients, and tolerance to niacin-induced flushing develops rapidly. Healthcare professionals should particularly address flushing during niacin dose titration.
Topics: Arachidonic Acid; Delayed-Action Preparations; Dyslipidemias; Flushing; Humans; Hypolipidemic Agents; Niacin; Patient Education as Topic; Prostaglandin Antagonists; Prostaglandins; Receptors, Immunologic; Receptors, Prostaglandin; Vasoconstriction; Vasodilation
PubMed: 19691622
DOI: 10.1111/j.1742-1241.2009.02099.x -
British Journal of Pharmacology Apr 2019In contrast to the availability of potent and selective antagonists of several prostaglandin receptor types (including DP , DP , EP and TP receptors), there has been a... (Review)
Review
In contrast to the availability of potent and selective antagonists of several prostaglandin receptor types (including DP , DP , EP and TP receptors), there has been a paucity of well-characterized, selective FP receptor antagonists. The earliest ones included dimethyl amide and dimethyl amine derivatives of PGF , but these have failed to gain prominence. The fluorinated PGF analogues, AL-8810 and AL-3138, were subsequently discovered as competitive and non-competitive FP receptor antagonists respectively. Non-prostanoid structures, such as the thiazolidinone AS604872, the D-amino acid-based oligopeptide PDC31 and its peptidomimic analogue PDC113.824 came next, but the latter two are allosteric inhibitors of FP receptor signalling. AL-8810 has a sub-micromolar in vitro potency and ≥2 log unit selectivity against most other PG receptors when tested in several cell- and tissue-based functional assays. Additionally, AL-8810 has demonstrated therapeutic efficacy as an FP receptor antagonist in animal models of stroke, traumatic brain injury, multiple sclerosis, allodynia and endometriosis. Consequently, it appears that AL-8810 has become the FP receptor antagonist of choice. LINKED ARTICLES: This article is part of a themed section on Eicosanoids 35 years from the 1982 Nobel: where are we now? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.8/issuetoc.
Topics: Animals; Dinoprost; Drug Discovery; Humans; Prostaglandins F, Synthetic; Receptors, Prostaglandin
PubMed: 29679483
DOI: 10.1111/bph.14335 -
The Western Journal of Medicine Oct 1985Although prostaglandin research began about 50 years ago, many of the most important advances in understanding the biochemistry, physiology and pharmacology have taken... (Review)
Review
Although prostaglandin research began about 50 years ago, many of the most important advances in understanding the biochemistry, physiology and pharmacology have taken place within the past five to ten years. There is great potential for the extension of this research to the clinical practice of medicine. At this time, the most common interaction that clinicians have with the prostaglandin field is in administering nonsteroidal anti-inflammatory drugs, which function by inhibiting prostaglandins. The uses of these drugs include treating not only inflammation, but also dysmenorrhea, some renal disease, thrombotic diseases and some metabolic disorders. Prostaglandin analogs, with their potent effects on uterine contraction, are in common use in obstetrics. Other analogs, with gastric and duodenal cytoprotective effects are useful in treating peptic ulcer disease. Future benefits from prostaglandin and leukotriene research may include new therapy for inflammatory and hypersensitivity diseases such as asthma, inflammatory bowel diseases and dermatitis.
Topics: Animals; Anti-Inflammatory Agents; Cardiovascular Diseases; Chemical Phenomena; Chemistry; Digestive System; Digestive System Physiological Phenomena; Female; Humans; Immunity, Cellular; Inflammation; Kidney; Leukotriene B4; Lung; Lung Diseases; Male; Metabolic Diseases; Pregnancy; Prostaglandin Antagonists; Prostaglandins; Reproduction; SRS-A; Thromboxanes; Uterine Contraction
PubMed: 3004043
DOI: No ID Found -
Clinical Cardiology May 1981In parallel with experimental research into methods for salvage of ischemic myocardium after acute myocardial infarction (AMI) over the last decade, there has been a... (Review)
Review
In parallel with experimental research into methods for salvage of ischemic myocardium after acute myocardial infarction (AMI) over the last decade, there has been a growing interest in prostaglandins (PG) and their inhibition by aspirin-like drugs or nonsteroidal anti-inflammatory drugs (NSAID). The finding of enhanced PG release during myocardial ischemia and its blockade by the NSAID indomethacin led to the hypothesis that PG might influence the infarction process. Because PG differ in vasoactive, cellular, and metabolic properties, and PG inhibitors also differ in their ability to inhibit synthesis of different PG and their metabolites, some PG inhibitors might be expected to reduce myocardial ischemic injury and infarct size. In addition, the NSAID may directly modify cellular events during infarction. Experiments with NSAID in the anesthetized and conscious animals have demonstrated a reduction of myocardial infarct size with ibuprofen, but an increase in infarct size with indomethacin. The opposite effects of these agents on infarct size might have been related to the different doses used, different degrees of inhibition of PG and their metabolites, and different effects on factors influencing myocardial oxygen supply and demand, metabolic and cellular events during infarction. It has recently been suggested that some of these agents might also influence the healing process after AMI and, therefore, late complications.
Topics: Acute Disease; Animals; Aspirin; Coronary Disease; Humans; Ibuprofen; Indomethacin; Models, Biological; Myocardial Infarction; Prognosis; Prostaglandin Antagonists; Prostaglandins
PubMed: 7021033
DOI: 10.1002/clc.4960040302 -
Diabetologia Jul 2020Inflammatory signals and increased prostaglandin synthesis play a role during the development of diabetes. The prostaglandin D (PGD) receptor, GPR44/DP2, is highly...
AIMS/HYPOTHESIS
Inflammatory signals and increased prostaglandin synthesis play a role during the development of diabetes. The prostaglandin D (PGD) receptor, GPR44/DP2, is highly expressed in human islets and activation of the pathway results in impaired insulin secretion. The role of GPR44 activation on islet function and survival rate during chronic hyperglycaemic conditions is not known. In this study, we investigate GPR44 inhibition by using a selective GPR44 antagonist (AZ8154) in human islets both in vitro and in vivo in diabetic mice transplanted with human islets.
METHODS
Human islets were exposed to PGD or proinflammatory cytokines in vitro to investigate the effect of GPR44 inhibition on islet survival rate. In addition, the molecular mechanisms of GPR44 inhibition were investigated in human islets exposed to high concentrations of glucose (HG) and to IL-1β. For the in vivo part of the study, human islets were transplanted under the kidney capsule of immunodeficient diabetic mice and treated with 6, 60 or 100 mg/kg per day of a GPR44 antagonist starting from the transplantation day until day 4 (short-term study) or day 17 (long-term study) post transplantation. IVGTT was performed on mice at day 10 and day 15 post transplantation. After termination of the study, metabolic variables, circulating human proinflammatory cytokines, and hepatocyte growth factor (HGF) were analysed in the grafted human islets.
RESULTS
PGD or proinflammatory cytokines induced apoptosis in human islets whereas GPR44 inhibition reversed this effect. GPR44 inhibition antagonised the reduction in glucose-stimulated insulin secretion induced by HG and IL-1β in human islets. This was accompanied by activation of the Akt-glycogen synthase kinase 3β signalling pathway together with phosphorylation and inactivation of forkhead box O-1and upregulation of pancreatic and duodenal homeobox-1 and HGF. Administration of the GPR44 antagonist for up to 17 days to diabetic mice transplanted with a marginal number of human islets resulted in reduced fasting blood glucose and lower glucose excursions during IVGTT. Improved glucose regulation was supported by increased human C-peptide levels compared with the vehicle group at day 4 and throughout the treatment period. GPR44 inhibition reduced plasma levels of TNF-α and growth-regulated oncogene-α/chemokine (C-X-C motif) ligand 1 and increased the levels of HGF in human islets.
CONCLUSIONS/INTERPRETATION
Inhibition of GPR44 in human islets has the potential to improve islet function and survival rate under inflammatory and hyperglycaemic stress. This may have implications for better survival rate of islets following transplantation.
Topics: Apoptosis; Blotting, Western; Cell Death; DNA-Binding Proteins; Glucose; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Prostaglandin D2; Real-Time Polymerase Chain Reaction; Receptors, Immunologic; Receptors, Prostaglandin; Transcription Factors
PubMed: 32350565
DOI: 10.1007/s00125-020-05138-z -
BMJ (Clinical Research Ed.) Oct 2012To determine the most effective tocolytic agent at delaying delivery. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine the most effective tocolytic agent at delaying delivery.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Cochrane Central Register of Controlled Trials, Medline, Medline In-Process, Embase, and CINAHL up to 17 February 2012.
STUDY SELECTION
Randomised controlled trials of tocolytic therapy in women at risk of preterm delivery.
DATA EXTRACTION
At least two reviewers extracted data on study design, characteristics, number of participants, and outcomes reported (neonatal and maternal). A network meta-analysis was done using a random effects model with drug class effect. Two sensitivity analyses were carried out for the primary outcome; restricted to studies at low risk of bias and restricted to studies excluding women at high risk of preterm delivery (those with multiple gestation and ruptured membranes).
RESULTS
Of the 3263 titles initially identified, 95 randomized controlled trials of tocolytic therapy were reviewed. Compared with placebo, the probability of delivery being delayed by 48 hours was highest with prostaglandin inhibitors (odds ratio 5.39, 95% credible interval 2.14 to 12.34) followed by magnesium sulfate (2.76, 1.58 to 4.94), calcium channel blockers (2.71, 1.17 to 5.91), beta mimetics (2.41, 1.27 to 4.55), and the oxytocin receptor blocker atosiban (2.02, 1.10 to 3.80). No class of tocolytic was significantly superior to placebo in reducing neonatal respiratory distress syndrome. Compared with placebo, side effects requiring a change of medication were significantly higher for beta mimetics (22.68, 7.51 to 73.67), magnesium sulfate (8.15, 2.47 to 27.70), and calcium channel blockers (3.80, 1.02 to 16.92). Prostaglandin inhibitors and calcium channel blockers were the tocolytics with the best probability of being ranked in the top three medication classes for the outcomes of 48 hour delay in delivery, respiratory distress syndrome, neonatal mortality, and maternal side effects (all cause).
CONCLUSIONS
Prostaglandin inhibitors and calcium channel blockers had the highest probability of delaying delivery and improving neonatal and maternal outcomes.
Topics: Calcium Channel Blockers; Female; Humans; Magnesium Sulfate; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prostaglandin Antagonists; Randomized Controlled Trials as Topic; Time Factors; Tocolysis; Tocolytic Agents; Treatment Outcome; Vasotocin
PubMed: 23048010
DOI: 10.1136/bmj.e6226 -
British Journal of Clinical Pharmacology Aug 2018Preterm birth remains a significant risk for later disability. The selective inhibition of the prostaglandin F receptor has significant advantages for a tocolytic. The... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Preterm birth remains a significant risk for later disability. The selective inhibition of the prostaglandin F receptor has significant advantages for a tocolytic. The prodrug OBE022 and its metabolite OBE002 are novel prostaglandin F receptor antagonists under development for treating preterm labour.
METHODS
We performed a prospective, first in human, Phase I, dose escalation, placebo-controlled, randomized trial at a clinical trial site in the UK. Placebo, single ascending doses of 10, 30, 100, 300, 1000 or 1300 mg, and multiple ascending doses over 7 days of 100, 300 or 1000 mg day ; were administered to postmenopausal female volunteers. Food interaction was additionally evaluated.
RESULTS
Subjects tolerated OBE022 well at all single and multiple doses. No clinically relevant changes in safety parameters were shown and there were no serious adverse events. Observations showed that prodrug OBE022 was readily absorbed and rapidly converted into its equally active stable metabolite OBE002. The plasma level of OBE002 rose with increasing doses, reaching exposure levels that were anticipated to be clinically relevant within 1 h following administration. There was no clinically significant food interaction, with peak exposures reduced to 80% and area under the curve staying bioequivalent. The mean half-life of OBE002 ranged between 8 and 11 h following administration of a single dose and 22-29 h after multiple doses.
CONCLUSIONS
Administration of OBE022 was safe and had favourable pharmacokinetic characteristics and no clinically relevant interaction with food. Our results allow further investigation of OBE022 in preterm labour patients.
Topics: Administration, Oral; Area Under Curve; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Esters; Female; Food-Drug Interactions; Healthy Volunteers; Humans; Middle Aged; Obstetric Labor, Premature; Postmenopause; Pregnancy; Prodrugs; Prospective Studies; Receptors, Prostaglandin; Sulfones; Thiazolidines; Tocolytic Agents
PubMed: 29708281
DOI: 10.1111/bcp.13622 -
Molecular Medicine Reports Oct 2020Prostaglandin E2 (PGE2) is involved in numerous physiological and pathological processes of the kidney via its four receptors. A previous study has suggested that a...
Prostaglandin E2 (PGE2) is involved in numerous physiological and pathological processes of the kidney via its four receptors. A previous study has suggested that a defect in the PGE2 receptor 1 (EP1) gene markedly suppressed the transforming growth factor‑β1 (TGF‑β1)‑induced mesangial cell (MC) proliferation and extracellular matrix aggregation. Therefore, the present study aimed to adopt a pharmacological method of specifically suppressing or activating the EP1 receptor to further verify and demonstrate these results. The EP1 receptor antagonist SC‑19220 and EP1 receptor agonist 17‑phenyl‑trinor‑PGE2 ethyl amide (17‑pt‑PGE2) were selectively used to treat five‑sixths nephrectomy renal fibrosis model mice and TGF‑β1‑stimulated MCs. An Alpha screen PGE2 assay kit, flow cytometry, western blotting and immunohistochemical techniques were adopted to perform in vivo and in vitro experiments. The present results suggested that compared with the control group, the selective EP1 receptor antagonist SC‑19220 improved renal function, markedly reduced the plasma blood urea nitrogen and creatinine levels (P<0.05) and alleviated glomerulosclerosis (P<0.05). By contrast, the EP1 receptor agonist 17‑pt‑PGE2 aggravated renal dysfunction and glomerulosclerosis (P<0.05). To verify the renal protection mechanisms mediated by suppression of the EP1 receptor, the expression levels of endoplasmic reticulum stress (ERS)‑related proteins, including chaperone glucose‑regulated protein 78 (GRP78), transient receptor potential channel 1 (TRPC1) and protein kinase R‑like endoplasmic reticulum kinase (PERK), were further evaluated histologically. The expression of GRP78, TRPC1 and PERK in the antagonist treatment group were markedly downregulated (P<0.05), whereas those in the agonist treatment group were upregulated (P<0.05). The present in vitro experiments demonstrated that, compared with the control group, the EP1 receptor antagonist suppressed the expression of GRP78, TRPC1 and PERK (P<0.05), reduced the production of PGE2 (P<0.05) and decreased the MC apoptosis rate (P<0.05), thus alleviating TGF‑β1‑stimulated MC injury. Consequently, consistent with previous results, selectively antagonizing the EP1 receptor improved renal function and mitigated glomerulosclerosis, and its potential mechanism might be associated with the suppression of ERS.
Topics: Animals; Apoptosis; Cells, Cultured; Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide; Dinoprostone; Disease Models, Animal; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Glomerulonephritis; Heat-Shock Proteins; Kidney; Male; Mesangial Cells; Mice; Mice, Inbred C57BL; Nephrectomy; Prostaglandin Antagonists; Receptors, Prostaglandin E, EP1 Subtype; TRPC Cation Channels; Transforming Growth Factor beta1; eIF-2 Kinase
PubMed: 32700746
DOI: 10.3892/mmr.2020.11353