Original Article
Activation of corticotropin-releasing hormone system in the locus ceruleus induces the visceral sensitivity of irritable bowel syndrome rats
Wang Xi, Li Meng, Hu Yue, Dai Chunyan, Fu Yufei, Jin Weiyang, Chen Zhe, Lyu Bin
Published 2020-01-15
Cite as Chin J Dig, 2020,40(01): 40-44. DOI: 10.3760/cma.j.issn.0254-1432.2020.01.008
Abstract
ObjectiveTo study the role of corticotropin-releasing hormone (CRH) system in locus ceruleus (LC) in irritable bowel syndrome (IBS) and to explore its molecular mechanism.
MethodsThe IBS rat was established by maternal separation following with postnatal stress. The tissues sample of LC was obtained by micropunched nuclei. The expression of c-Fos, CRH and its receptors including corticotropin-releasing hormone receptor (CRHR) 1 and CRHR2 of rats’ LC tissues of control group and IBS group was detected by quantitative polymerase chain reaction(PCR). The expression of DNA methyltransferase (DNTM) 1, DNMT3a and DNMT3b at the mRNA level were also measured. In addition, the expression of histone methyltransferase ASH2-like protein (ASH2L) and SET and MYND domain containing 2 (SMYD2) was determined by Western blotting. T test was used for statistical analysis.
ResultsThe rectal pneumatic pressure of IBS group was lower than that of control group ((69.82±5.47) mmHg vs. (86.86±5.98) mmHg; 1 mmHg=0.133 kPa), however compared with that of control group, the expression of c-Fos at the mRNA level increased (2.11±0.44 vs.1.00±0.19), and the differences were statistically significant (t=6.215 and 2.321, P<0.01 and 0.05). In addition, compared with that of control group, the expression of CRH at the mRNA level increased (1.99±0.35 vs.1.00±0.13), and the difference was statistically significant (t= 2.797, P<0.05). Compared with that of control group, the expression of SMYD2 at the protein level up-regulated (1.04±0.21 vs. 0.61±0.12), and the difference was statistically significant (t=4.451, P<0.01). However, there were no statistically significant differences in the expression of CRHR-1, CRHR2, DNMT1, DNMT3a, DNMT3b at the mRNA level, and the expression of ASH2L between IBS group and control group (0.96±0.13 vs. 1.00±0.26, 1.35±0.63 vs. 1.00±0.43, 1.40±0.61 vs.1.00±0.19, 1.39±0.58 vs. 1.00±0.21, 1.45±0.71vs.1.00±0.39 and 0.80±0.19 vs. 1.05±0.26, respectively; all P>0.05).
ConclusionsMaternal separation combined with postnatal stress affect the transcription of Crh gene in LC and cause the activation of the stress regulation network CRH and norepinephrine system, resulting in the increase of the visceral sensitivity of rats. The abnormal transcription of Crh gene may be related with SMYD2-mediated histone H3K36 methylation, but not related with the modification of DNA methylation.
Key words:
Irritable bowel syndrome; Locus ceruleus; Maternal separation stress; Corticotropin-releasing hormone system; Epigenetics
Contributor Information
Wang Xi
Key Laboratory of Digestive Pathophysiology of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China
Li Meng
Key Laboratory of Digestive Pathophysiology of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China
Hu Yue
Key Laboratory of Digestive Pathophysiology of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China
Dai Chunyan
Key Laboratory of Digestive Pathophysiology of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China
Fu Yufei
Key Laboratory of Digestive Pathophysiology of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China
Jin Weiyang
College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310036, China
Chen Zhe
Key Laboratory of Digestive Pathophysiology of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China
Lyu Bin
Key Laboratory of Digestive Pathophysiology of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China
