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Mucosa repair mechanisms of Tong-Xie-Yao-Fang mediated by CRH-R2 in murine, dextran sulfate sodium-induced colitis.
World J Gastroenterol. 2018 Apr 28; 24(16):1766-1778.WJ

Abstract

AIM

To explore the significance of corticotropin-releasing hormone (CRH)-receptor (R)2 in mucosal healing of dextran sulfate sodium (DSS)-induced colitis and the effect of Tong-Xie-Yao-Fang (TXYF) on CRH-R2 expression and regulation.

METHODS

Ulcerative colitis was induced in mice by administration of 3% (w/v) DSS for 7 d. Once the model was established, mice were administered urocortin-2 (30 μg/kg), a peptide which binds exclusively to CRH-R2, or various doses of aqueous TXYF extracts (2.8-11.2 g/kg), a CRH-R2 antagonist Astressin (Ast)2B (20 μg/kg), Ast2B + Ucn2, or Ast2B with various doses of aqueous TXYF extracts for 9 d. Colonic mucosal permeability was then evaluated by measuring the fluorescence intensity in serum. The colitis disease activity index (DAI), histology, body weight loss and colon length were assessed to evaluate the condition of colitis. Terminal deoxynucleotidyl transferase dUTP nick-end labeling was used to detect apoptosis of the intestinal epithelial cells. The expression level of Ki-67 represented the proliferation of colonic epithelial cells and was detected by immunohistochemistry. The expression levels of inflammation cytokines IL-6, TNF-α and CXCL-1 were examined in colon tissues using real-time PCR and ELISA kits.

RESULTS

Compared with the DSS group, mice treated with the CRH-R2 antagonist Ast2B showed greater loss of body weight, shorter colon lengths (4.90 ± 0.32 vs 6.21 ± 0.34 cm, P < 0.05), and higher DAI (3.61 ± 0.53 vs 2.42 ± 0.32, P < 0.05) and histological scores (11.50 ± 1.05 vs 8.33 ± 1.03, P < 0.05). Additionally, the Ast2B group showed increased intestinal permeability (2.76 ± 0.11 μg/mL vs 1.47 ± 0.11 μg/mL, P < 0.001), improved secretion of inflammatory cytokines in colon tissue, and reduced colonic epithelial cell proliferation (4.97 ± 4.25 vs 22.51 ± 8.22, P < 0.05). Increased apoptosis (1422.39 ± 90.71 vs 983.01 ± 98.17, P < 0.001) was also demonstrated. The Ucn2 group demonstrated lower DAI (0.87 ± 0.55 vs 2.42 ± 0.32, P < 0.001) and histological scores (4.33 ± 1.50 vs 8.33 ± 1.03, P < 0.05). Diminished weight loss, longer colon length (9.58 ± 0.62 vs 6.21 ± 0.34 cm, P < 0.001), reduced intestinal permeability (0.75 ± 0.07 vs 1.47 ± 0.11 μg/mL, P < 0.001), inhibited secretion of inflammatory cytokines in colon tissue and increased colonic epithelial cell proliferation (90.04 ± 15.50 vs 22.51 ± 8.22, P < 0.01) were all observed. Reduced apoptosis (149.55 ± 21.68 vs 983.01 ± 98.17, P < 0.05) was also observed. However, significant statistical differences in the results of the Ast2B group and Ast2B + Ucn2 group were observed. TXYF was also found to ameliorate symptoms of DSS-induced colitis in mice and to promote mucosal repair like Ucn2. There were significant differences between the Ast2B + TXYF groups and the TXYF groups.

CONCLUSION

CRH-R2 activates the intestinal mucosal antiinflammatory response by regulating migration, proliferation and apoptosis of intestinal epithelial cells in colitis-induced mice, and plays an important antiinflammatory role. TXYF promotes mucosal repair in colitis mice by regulating CRH-R2.

Authors+Show Affiliations

The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China.Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China. yhfansjr@163.com.The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China.The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China.Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China.Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China.The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China.The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29713130

Citation

Gong, Shan-Shan, et al. "Mucosa Repair Mechanisms of Tong-Xie-Yao-Fang Mediated By CRH-R2 in Murine, Dextran Sulfate Sodium-induced Colitis." World Journal of Gastroenterology, vol. 24, no. 16, 2018, pp. 1766-1778.
Gong SS, Fan YH, Wang SY, et al. Mucosa repair mechanisms of Tong-Xie-Yao-Fang mediated by CRH-R2 in murine, dextran sulfate sodium-induced colitis. World J Gastroenterol. 2018;24(16):1766-1778.
Gong, S. S., Fan, Y. H., Wang, S. Y., Han, Q. Q., Lv, B., Xu, Y., Chen, X., & He, Y. E. (2018). Mucosa repair mechanisms of Tong-Xie-Yao-Fang mediated by CRH-R2 in murine, dextran sulfate sodium-induced colitis. World Journal of Gastroenterology, 24(16), 1766-1778. https://doi.org/10.3748/wjg.v24.i16.1766
Gong SS, et al. Mucosa Repair Mechanisms of Tong-Xie-Yao-Fang Mediated By CRH-R2 in Murine, Dextran Sulfate Sodium-induced Colitis. World J Gastroenterol. 2018 Apr 28;24(16):1766-1778. PubMed PMID: 29713130.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mucosa repair mechanisms of Tong-Xie-Yao-Fang mediated by CRH-R2 in murine, dextran sulfate sodium-induced colitis. AU - Gong,Shan-Shan, AU - Fan,Yi-Hong, AU - Wang,Shi-Yi, AU - Han,Qing-Qing, AU - Lv,Bin, AU - Xu,Yi, AU - Chen,Xi, AU - He,Yao-Er, PY - 2018/02/12/received PY - 2018/03/14/revised PY - 2018/03/31/accepted PY - 2018/5/2/entrez PY - 2018/5/2/pubmed PY - 2018/9/28/medline KW - Aqueous extracts KW - Astressin 2B KW - Corticotropin-releasing hormone receptor 2 KW - Mucosal healing KW - Tong-Xie-Yao-Fang KW - Ulcerative colitis KW - Urocortin 2 SP - 1766 EP - 1778 JF - World journal of gastroenterology JO - World J. Gastroenterol. VL - 24 IS - 16 N2 - AIM: To explore the significance of corticotropin-releasing hormone (CRH)-receptor (R)2 in mucosal healing of dextran sulfate sodium (DSS)-induced colitis and the effect of Tong-Xie-Yao-Fang (TXYF) on CRH-R2 expression and regulation. METHODS: Ulcerative colitis was induced in mice by administration of 3% (w/v) DSS for 7 d. Once the model was established, mice were administered urocortin-2 (30 μg/kg), a peptide which binds exclusively to CRH-R2, or various doses of aqueous TXYF extracts (2.8-11.2 g/kg), a CRH-R2 antagonist Astressin (Ast)2B (20 μg/kg), Ast2B + Ucn2, or Ast2B with various doses of aqueous TXYF extracts for 9 d. Colonic mucosal permeability was then evaluated by measuring the fluorescence intensity in serum. The colitis disease activity index (DAI), histology, body weight loss and colon length were assessed to evaluate the condition of colitis. Terminal deoxynucleotidyl transferase dUTP nick-end labeling was used to detect apoptosis of the intestinal epithelial cells. The expression level of Ki-67 represented the proliferation of colonic epithelial cells and was detected by immunohistochemistry. The expression levels of inflammation cytokines IL-6, TNF-α and CXCL-1 were examined in colon tissues using real-time PCR and ELISA kits. RESULTS: Compared with the DSS group, mice treated with the CRH-R2 antagonist Ast2B showed greater loss of body weight, shorter colon lengths (4.90 ± 0.32 vs 6.21 ± 0.34 cm, P < 0.05), and higher DAI (3.61 ± 0.53 vs 2.42 ± 0.32, P < 0.05) and histological scores (11.50 ± 1.05 vs 8.33 ± 1.03, P < 0.05). Additionally, the Ast2B group showed increased intestinal permeability (2.76 ± 0.11 μg/mL vs 1.47 ± 0.11 μg/mL, P < 0.001), improved secretion of inflammatory cytokines in colon tissue, and reduced colonic epithelial cell proliferation (4.97 ± 4.25 vs 22.51 ± 8.22, P < 0.05). Increased apoptosis (1422.39 ± 90.71 vs 983.01 ± 98.17, P < 0.001) was also demonstrated. The Ucn2 group demonstrated lower DAI (0.87 ± 0.55 vs 2.42 ± 0.32, P < 0.001) and histological scores (4.33 ± 1.50 vs 8.33 ± 1.03, P < 0.05). Diminished weight loss, longer colon length (9.58 ± 0.62 vs 6.21 ± 0.34 cm, P < 0.001), reduced intestinal permeability (0.75 ± 0.07 vs 1.47 ± 0.11 μg/mL, P < 0.001), inhibited secretion of inflammatory cytokines in colon tissue and increased colonic epithelial cell proliferation (90.04 ± 15.50 vs 22.51 ± 8.22, P < 0.01) were all observed. Reduced apoptosis (149.55 ± 21.68 vs 983.01 ± 98.17, P < 0.05) was also observed. However, significant statistical differences in the results of the Ast2B group and Ast2B + Ucn2 group were observed. TXYF was also found to ameliorate symptoms of DSS-induced colitis in mice and to promote mucosal repair like Ucn2. There were significant differences between the Ast2B + TXYF groups and the TXYF groups. CONCLUSION: CRH-R2 activates the intestinal mucosal antiinflammatory response by regulating migration, proliferation and apoptosis of intestinal epithelial cells in colitis-induced mice, and plays an important antiinflammatory role. TXYF promotes mucosal repair in colitis mice by regulating CRH-R2. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/29713130/Mucosa_repair_mechanisms_of_Tong_Xie_Yao_Fang_mediated_by_CRH_R2_in_murine_dextran_sulfate_sodium_induced_colitis_ L2 - http://www.wjgnet.com/1007-9327/full/v24/i16/1766.htm DB - PRIME DP - Unbound Medicine ER -