Limits...
Increased production of BDNF in colonic epithelial cells induced by fecal supernatants from diarrheic IBS patients.

Wang P, Chen FX, Du C, Li CQ, Yu YB, Zuo XL, Li YQ - Sci Rep (2015)

Bottom Line: 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.We found a significant increase in PAR-2 expression in Caco-2 after IBS-D FSN stimulation.Moreover, we found that phosphorylation of p38 MAPK, not NF-κB p65, contributed to PAR-2-mediated BDNF overexpression.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, P.R. China [2] Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, P.R. China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Serine protease activity was increased in fecal supernatants (FSN) from IBS-D patients.The serine protease inhibitor FUT-175 markedly inhibited protease activity released from IBS-D FSN (n = 17 for HC FSN, n = 22 for IBS-D FSN. ***P < 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4441152&req=5

f1: Serine protease activity was increased in fecal supernatants (FSN) from IBS-D patients.The serine protease inhibitor FUT-175 markedly inhibited protease activity released from IBS-D FSN (n = 17 for HC FSN, n = 22 for IBS-D FSN. ***P < 0.001).

Mentions: Total fecal protease activity in IBS-D patients (1461 ± 143.1 U/mg of protein) was approximately 3-fold greater than that in healthy controls (HCs) (438.6 ± 70.2 U/mg of protein). Preincubation of IBS-D FSN with the serine protease inhibitor FUT-175 significantly reduced the proteolytic activity close to that of HCs, which suggests that the increased proteolytic activity in IBS-D FSN is dependent on serine protease (Fig. 1).


Increased production of BDNF in colonic epithelial cells induced by fecal supernatants from diarrheic IBS patients.

Wang P, Chen FX, Du C, Li CQ, Yu YB, Zuo XL, Li YQ - Sci Rep (2015)

Serine protease activity was increased in fecal supernatants (FSN) from IBS-D patients.The serine protease inhibitor FUT-175 markedly inhibited protease activity released from IBS-D FSN (n = 17 for HC FSN, n = 22 for IBS-D FSN. ***P < 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4441152&req=5

f1: Serine protease activity was increased in fecal supernatants (FSN) from IBS-D patients.The serine protease inhibitor FUT-175 markedly inhibited protease activity released from IBS-D FSN (n = 17 for HC FSN, n = 22 for IBS-D FSN. ***P < 0.001).
Mentions: Total fecal protease activity in IBS-D patients (1461 ± 143.1 U/mg of protein) was approximately 3-fold greater than that in healthy controls (HCs) (438.6 ± 70.2 U/mg of protein). Preincubation of IBS-D FSN with the serine protease inhibitor FUT-175 significantly reduced the proteolytic activity close to that of HCs, which suggests that the increased proteolytic activity in IBS-D FSN is dependent on serine protease (Fig. 1).

Bottom Line: 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.We found a significant increase in PAR-2 expression in Caco-2 after IBS-D FSN stimulation.Moreover, we found that phosphorylation of p38 MAPK, not NF-κB p65, contributed to PAR-2-mediated BDNF overexpression.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, P.R. China [2] Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, P.R. China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus