Increased production of BDNF in colonic epithelial cells induced by fecal supernatants from diarrheic IBS patients.
Increased production of BDNF in colonic epithelial cells induced by fecal supernatants from diarrheic IBS patients.
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腹泻性 IBS 患者粪便上清液诱导结肠上皮细胞中 BDNF 的产生增加。
DOI：
10.1038/srep10121
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发表时间：
2015-05-22
影响因子：
4.6
通讯作者：
Li YQ
中科院分区：
文献类型：
--
作者：
Wang P;Chen FX;Du C;Li CQ;Yu YB;Zuo XL;Li YQ
Colonic brain-derived neurotrophic factor (BDNF) plays an essential role in pathogenesis of abdominal pain in diarrhea-predominant irritable bowel syndrome (IBS-D), but regulation on its expression remains unclear. We investigated the role of fecal supernatants (FSN) from IBS-D patients on regulating BDNF expression in colonic epithelial cells of human and mice. Using human Caco-2 cells, we found that IBS-D FSN significantly increased BDNF mRNA and protein levels compared to control FSN, which were remarkably suppressed by the serine protease inhibitor. To further explore the potential mechanisms, we investigated the impact of protease-activated receptor-2 (PAR-2) on BDNF expression. We found a significant increase in PAR-2 expression in Caco-2 after IBS-D FSN stimulation. Knockdown of PAR-2 significantly inhibited IBS-D FSN-induced upregulation of BDNF. Moreover, we found that phosphorylation of p38 MAPK, not NF-κB p65, contributed to PAR-2-mediated BDNF overexpression. To confirm these results, we intracolonically infused IBS-D or control FSN in mice and found that IBS-D FSN significantly elevated colonic BDNF and visceral hypersensitivity in mice, which were both suppressed by the inhibitor of serine protease or antagonist of PAR-2. Together, our data indicate that activation of PAR-2 signaling by IBS-D FSN promotes expression of colonic BDNF, thereby contributing to IBS-like visceral hypersensitivity.
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DOI：
10.1124/jpet.111.187062
发表时间：
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影响因子：
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作者：
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