AIM： To investigate EP4-selective agonist effect on indomethacin-induced gastric lesions and on the spontaneous healing of chronic gastric ulcers. METHODS： In a mouse model of gastric bleeding with high dose of indo...AIM： To investigate EP4-selective agonist effect on indomethacin-induced gastric lesions and on the spontaneous healing of chronic gastric ulcers. METHODS： In a mouse model of gastric bleeding with high dose of indomethacin （20 mg/kg）, an EP4-selective agonist was administered orally. Stomach lesions and gastric mucous regeneration were monitored. In a mouse model of chronic gastric ulcer induced by acetic acid, EP4 agonist effect on the healing of chronic gastric ulcer was evaluated in the presence or absence of low dose indomethadn （3 mg/kg）. In cultured human gastric mucous cells, EP4 agonist effect on indomethacin- induced apoptosis was assessed by flow cytometry. RESULTS： The EP4-selective agonist reduced high dose indomethacin-induced acute hemorrhagic damage and promoted mucous epithelial regeneration. Low-dose indomethacin aggravated ulcer bleeding and inflammation, and delayed the healing of the established chronic gastric ulcer. The EP4 agonist, when applied locally, not only offset indomethacin-induced gastric bleeding and inflammation, but also accelerated ulcer healing. In the absence of indomethacin, the EP4 agonist even accelerated chronic gastric ulcer healing and suppressed inflammatory cell infiltration in the granulation tissue. In vitro, the EP4 agonist protected human gastric mucous cells from indomethacin-induced apoptosis.CONCLUSION： EP4-selective agonist may prevent indomethacin-induced gastric lesions and promote healing of existing and i ulcers, via promoting mucous epithelial cells. proliferation and survival of mucous epithelial cells.展开更多
Fever is an adaptive host response coordinated by the central nervous system （CNS） during systemic immune challenge. Recent research shed light on the mechanism of fever generation, particularly the underlying neura...Fever is an adaptive host response coordinated by the central nervous system （CNS） during systemic immune challenge. Recent research shed light on the mechanism of fever generation, particularly the underlying neural pathways. In this review, we first briefly summarize current views on the mechanism of sensing microbial infection by the nervous system, and the roles of prostaglandin E2 （PGE2） and its receptors in fever; then we focus on the neural circuits underlying fever generation, particularly their relationship with the distribution of PGE2 receptors within the CNS. At the end, an overall neurochemical model of fever generation is presented, pointing to the direction for future studies.展开更多
Objective To determine the expression of E-prostanoid1 (EP 1) and F-prostanoid (FP) receptor mRNAs in iris-ciliary bodies of the human eye using in situ hybridization.Methods EP 1 and FP receptor mRNAs were detect...Objective To determine the expression of E-prostanoid1 (EP 1) and F-prostanoid (FP) receptor mRNAs in iris-ciliary bodies of the human eye using in situ hybridization.Methods EP 1 and FP receptor mRNAs were detected by riboprobes labeled with digoxigenin on paraffin sections of the iris-ciliary body tissue of the human eye using in situ hybridization. Results EP 1 and FP receptor mRNAs were highly expressed in blood vessels, muscles and the endothelia of the iris. EP 1 receptor hybridization signals were present in all muscle fibers of the ciliary body. Hybridization signal corresponding to FP receptor mRNA transcript was predominantly expressed in the circular muscle and in the collagenous connective tissues of the ciliary body. FP receptor mRNA was not detected in radial and longitudinal muscles. Conclusions EP 1 and FP receptor mRNAs in human ocular tissues appear to be widely localized in the functional sites of the respective receptor agonists. Selective localization of EP 1 and FP receptor mRNAs in the circular muscles and collagenous connective tissues of the ciliary body suggests that EP 1 and FP receptors play an important role in enhancing uveoscleral outflow of aqueous humor.展开更多
Among the four prostaglandin E2 receptors,EP3 receptor is the one most abundantly expressed in white adipose tissue(WAT).The mouse EP3 gene gives rise to three isoforms,namely EP3α,EP3β,and EP3γ,which differ only a...Among the four prostaglandin E2 receptors,EP3 receptor is the one most abundantly expressed in white adipose tissue(WAT).The mouse EP3 gene gives rise to three isoforms,namely EP3α,EP3β,and EP3γ,which differ only at their C-terminal tails.To date,functions of EP3 receptor and its isoforms in WAT remain incompletely characterized.In this study,we found that the expression of all EP3 isoforms were downregulated in WAT of both db/db and high-fat diet-induced obese mice.Genetic ablation of three EP3 receptor isoforms(EP3^(−/−)mice)or EP3αand EP3γisoforms with EP3βintact(EP3βmice)led to an obese phenotype with increased food intake,decreased motor activity,reduced insulin sensitivity,and elevated serum triglycerides.Since the differentiation of preadipocytes and mouse embryonic fibroblasts to adipocytes was markedly facilitated by either pharmacological blockade or genetic deletion/inhibition of EP3 receptor via the cAMP/PKA/PPARγpathway,increased adipogenesis may contribute to obesity in EP3^(−/−)and EP3βmice.Moreover,both EP3^(−/−)and EP3βmice had increased lipolysis in WAT mainly due to the activated cAMP/PKA/hormone-sensitive lipase pathway.Taken together,our findings suggest that EP3 receptor and itsαandγisoforms are involved in both adipogenesis and lipolysis and influence food intake,serum lipid levels,and insulin sensitivity.展开更多
[目的]检测前列腺素E2(prostaglandin E2,PGE2)通过G蛋白偶联前列腺素E受体1(prostaglandin E re-ceptor1,EP1)对腰椎软骨终板细胞生长的影响。[方法]常规方法培养腰椎软骨终板细胞;应用RT-PCR和蛋白免疫印迹技术检测细胞EP基因及蛋白...[目的]检测前列腺素E2(prostaglandin E2,PGE2)通过G蛋白偶联前列腺素E受体1(prostaglandin E re-ceptor1,EP1)对腰椎软骨终板细胞生长的影响。[方法]常规方法培养腰椎软骨终板细胞;应用RT-PCR和蛋白免疫印迹技术检测细胞EP基因及蛋白质表达水平。应用MTT实验评估EP1受体选择性激动剂17-P-T-PGE2和EP1受体选择性抑制剂SC 51322对细胞生长增殖的影响。[结果]RT-PCR和Western blotting实验检测结果表明,软骨终板细胞均表达EP1、EP2、EP3和EP4。MTT实验检测显示EP1受体激动剂17-P-T-PGE2可促进软骨终板细胞生长,EP1受体选择性抑制剂SC 51322可抑制PGE2促起的软骨终板细胞生长。[结论]PGE2引起的软骨终板细胞增殖可能与EP1信号转导通路激活相关。展开更多
文摘AIM： To investigate EP4-selective agonist effect on indomethacin-induced gastric lesions and on the spontaneous healing of chronic gastric ulcers. METHODS： In a mouse model of gastric bleeding with high dose of indomethacin （20 mg/kg）, an EP4-selective agonist was administered orally. Stomach lesions and gastric mucous regeneration were monitored. In a mouse model of chronic gastric ulcer induced by acetic acid, EP4 agonist effect on the healing of chronic gastric ulcer was evaluated in the presence or absence of low dose indomethadn （3 mg/kg）. In cultured human gastric mucous cells, EP4 agonist effect on indomethacin- induced apoptosis was assessed by flow cytometry. RESULTS： The EP4-selective agonist reduced high dose indomethacin-induced acute hemorrhagic damage and promoted mucous epithelial regeneration. Low-dose indomethacin aggravated ulcer bleeding and inflammation, and delayed the healing of the established chronic gastric ulcer. The EP4 agonist, when applied locally, not only offset indomethacin-induced gastric bleeding and inflammation, but also accelerated ulcer healing. In the absence of indomethacin, the EP4 agonist even accelerated chronic gastric ulcer healing and suppressed inflammatory cell infiltration in the granulation tissue. In vitro, the EP4 agonist protected human gastric mucous cells from indomethacin-induced apoptosis.CONCLUSION： EP4-selective agonist may prevent indomethacin-induced gastric lesions and promote healing of existing and i ulcers, via promoting mucous epithelial cells. proliferation and survival of mucous epithelial cells.
文摘Fever is an adaptive host response coordinated by the central nervous system （CNS） during systemic immune challenge. Recent research shed light on the mechanism of fever generation, particularly the underlying neural pathways. In this review, we first briefly summarize current views on the mechanism of sensing microbial infection by the nervous system, and the roles of prostaglandin E2 （PGE2） and its receptors in fever; then we focus on the neural circuits underlying fever generation, particularly their relationship with the distribution of PGE2 receptors within the CNS. At the end, an overall neurochemical model of fever generation is presented, pointing to the direction for future studies.
文摘Objective To determine the expression of E-prostanoid1 (EP 1) and F-prostanoid (FP) receptor mRNAs in iris-ciliary bodies of the human eye using in situ hybridization.Methods EP 1 and FP receptor mRNAs were detected by riboprobes labeled with digoxigenin on paraffin sections of the iris-ciliary body tissue of the human eye using in situ hybridization. Results EP 1 and FP receptor mRNAs were highly expressed in blood vessels, muscles and the endothelia of the iris. EP 1 receptor hybridization signals were present in all muscle fibers of the ciliary body. Hybridization signal corresponding to FP receptor mRNA transcript was predominantly expressed in the circular muscle and in the collagenous connective tissues of the ciliary body. FP receptor mRNA was not detected in radial and longitudinal muscles. Conclusions EP 1 and FP receptor mRNAs in human ocular tissues appear to be widely localized in the functional sites of the respective receptor agonists. Selective localization of EP 1 and FP receptor mRNAs in the circular muscles and collagenous connective tissues of the ciliary body suggests that EP 1 and FP receptors play an important role in enhancing uveoscleral outflow of aqueous humor.
基金supported by the National Basic Research Program of China(973 Program)(2012CB517504 to Y.-F.G.)the National Natural Science Foundation of China(81390351,81270275,81200511,and 81030003 to Y.-F.G.)+1 种基金National Institutes of Health grants(DK46205 to R.M.B.)the Swedish Research Council(to J.-A.G.),and Shenzhen Peacock Plan&JCYJ 20140418095735626.
文摘Among the four prostaglandin E2 receptors,EP3 receptor is the one most abundantly expressed in white adipose tissue(WAT).The mouse EP3 gene gives rise to three isoforms,namely EP3α,EP3β,and EP3γ,which differ only at their C-terminal tails.To date,functions of EP3 receptor and its isoforms in WAT remain incompletely characterized.In this study,we found that the expression of all EP3 isoforms were downregulated in WAT of both db/db and high-fat diet-induced obese mice.Genetic ablation of three EP3 receptor isoforms(EP3^(−/−)mice)or EP3αand EP3γisoforms with EP3βintact(EP3βmice)led to an obese phenotype with increased food intake,decreased motor activity,reduced insulin sensitivity,and elevated serum triglycerides.Since the differentiation of preadipocytes and mouse embryonic fibroblasts to adipocytes was markedly facilitated by either pharmacological blockade or genetic deletion/inhibition of EP3 receptor via the cAMP/PKA/PPARγpathway,increased adipogenesis may contribute to obesity in EP3^(−/−)and EP3βmice.Moreover,both EP3^(−/−)and EP3βmice had increased lipolysis in WAT mainly due to the activated cAMP/PKA/hormone-sensitive lipase pathway.Taken together,our findings suggest that EP3 receptor and itsαandγisoforms are involved in both adipogenesis and lipolysis and influence food intake,serum lipid levels,and insulin sensitivity.
