372 Silencing of Gene Expression for Corticotropin-Releasing Factor (CRF) in the Colon Attenuates Stress-Induced Acceleration of Colonic Transit in Rats

Liu, Sumei; Mei-hu, QU; Ren, Wei; Bhargava, Aditi; Chang, Jen-Chieh; Hoy, Julia J.; Wang, Guo-Du; Zou, Fie; Wang, Xiyu; Sun, Xiaohong; Xia, Yun; Wood, Jackie D.

doi:10.1016/s0016-5085(08)60235-8

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We therefore aimed to investigate if transient perturbation in expression of endogenous CRF in the gut is sufficient to change stress‐induced colonic motor and secretory responses. Preliminary reports of the results have been published in abstract form …”

Section: Introductionmentioning

confidence: 99%

Endogenous CRF in rat large intestine mediates motor and secretory responses to stress

Liu

Chang

Long

et al. 2015

Neurogastroenterology Motil

View full text Add to dashboard Cite

Background Corticotropin-releasing factor (CRF) mediates our body’s overall responses to stress. The role of central CRF in stress-stimulated colonic motility is well characterized. We hypothesized that transient perturbation in expression of enteric CRF is sufficient to change stress-induced colonic motor and secretory responses. Methods Sprague-Dawley rats (adult, male) were subjected to 1-h partial restraint stress (PRS) and euthanized at 0, 4, 8, and 24 h. CRF mRNA and peptide levels in the colon were quantified by real-time RT-PCR, enzyme immunoassay, and immunohistochemistry. Double-stranded RNA (dsRNA) designed to target CRF (dsCRF) was injected into the colonic wall to attain RNA interference (RNAi)-mediated inhibition of CRF mRNA expression. DsRNA for β-globin was used as a control (dsControl). Four days after dsRNA injection, rats were subjected to 1-h PRS. Fecal output was measured. Ussing chamber techniques were used to assess colonic mucosal ion secretion and transepithelial tissue conductance. Key Results Exposure to PRS elevated CRF expression and increased CRF release in the rat colon. Injection of dsCRF inhibited basal CRF expression and prevented the PRS-induced increase in CRF expression, whereas CRF expression in dsControl-injected colons remained high after PRS. In rats treated with dsControl, PRS caused a significant increase in fecal pellet output, colonic baseline ion secretion, and transepithelial tissue conductance. Inhibition of CRF expression in the colon prevented PRS-induced increase in fecal output, baseline ion secretion, and transepithelial tissue conductance. Conclusions & Inferences These results provide direct evidence that transient perturbation in peripherally expressed CRF prevents colonic responses to stress.

show abstract

Section: Introductionmentioning

confidence: 99%