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Inflammatory bowel disease(IBD)is a kind of chronic and non-specific inflammatory disease comprising Crohn’s disease(CD)and ulcerative colitis(UC),the etiology has not yet been clarified. Endothelin-1(ET-1)is an active polypeptide composed of 21 amino acid residues,which can constrict blood vessels by activating voltage-dependent Ca2 + channels in vascular smooth muscle cells. Studies have shown that ET-1 plays an important role in the pathogenesis of IBD. This article reviewed the progress in study on ET-1 in the pathogenesis of IBD.
RÉSUMÉ
Objective To observe the mRNA expressions of endothelin-1(ET-1) and endothelin A/B receptors (ETA/B) in tissue of benign prostatic hyperplasia treated by daily low-dose sildenafil.Methods A total of 32 patients with benign prostatic hyperplasia were randomly divided into two groups:treatment(25 mg sildenafi for 12 weeks,n=16) and control (no drug,n=16) groups.Immunohistochemical staining,ELISA and RT-PCR were used to detect the expression levels of ET-1 protein and ET A/B mRNA,respectively.Results The expressions of ET-1 protein and ET A/B mRNA in prostatic tissue were significantly lower in treatment group than in control group[(53.31±18.56) ng/kg vs.(83.34±31.38) ng/kg,0.356±0.056 vs.0.624±0.083,0.721±0.083 vs.0.933±0.905,t=-3.295,10.715,6.937,all P＜0.001].Conclusions Daily low-dose sildenafil can reduce the expressions of ET-1 and ET A/B receptors mRNA in benign prostatic hyperplasia.
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Objective To investigate the modulation of ET-3 on the nuclear factor (NF)-κB/Bfl-1 antiapoptotic pathway in a malignant melanoma cell line A375. Methods Flow cytometry was performed to detect the apoptosis in cultured A375 cells after treatment with ET-3 of 100 nmol/L for 24 hours. ET-3 of various concentrations (0, 1, 10, 100 nmol/L) was used to treat some A375 cells with or without the pretreatment with the ETRB antagonist BQ788; after another 24-hour culture, RT-PCR and Western blot were conducted to examine the mRNA expression of Bfl-1 and protein expressions of Bfl-1 and ETRB, respectively. Results The 24-hour treatment with ET-3 of 100 nmol/L significantly reduced the apoptosis rate of A375 cells (F = 10.68, P ＜0.05). The mRNA and protein expressions of Bfl-1 were up-regulated by ET-3 in a concentration dependent manner (both P ＜ 0.01 ), while BQ788 significantly blocked the ET-3-induced up-regulation (F = 420.38,229.49, both P ＜ 0.01 ). The protein expression of pNF-κB in A375 cells was also enhanced by ET-3 of different concentrations (all P ＜ 0.05), but the enhancement was suppressed by BQ788, and there was a significant difference in the protein expression of pNF-κB between cells treated with ET-3 of 100 nmol/L and those treated with the combination of ET-3 of 100 nmol/L and BQ788 (F = 255.46, P ＜ 0.01 ). Conclusion ET-3/ETRB inhibits the apoptosis in A375 cells likely by activating the NF-κB/Bfl-1 anti-apoptotic pathway.