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2,4,6-trinitrobenzene sulfonic acid-induced chronic colitis with fibrosis and modulation of TGF-β1 signaling.
World J Gastroenterol 2014; 20(48):18207-15WJ

Abstract

AIM

To investigate whether targeting proteasome might reverse intestinal fibrosis in rats.

METHODS

Chronic colitis was induced in rats by repeated administration of increasing dose of 2,4,6-trinitrobenzene sulfonic acid (TNBS, 15, 30, 45, 60, 60, 60 mg) by rectal injection for 6 wk (from day 0 to day 35), while control rats received the vehicle. TNBS + bortezomib (BTZ) rats received intraperitoneal injections of BTZ twice weekly (from day 37 to day 44) at a dose of 25 mg/kg, whereas the control and TNBS groups received the same amount of the vehicle. Histologic scoring of inflammation and fibrosis was performed. Colonic production of transforming growth factor (TGF)-β was measured by ELISA. Colon fibrosis-related proteins such as phospho-p38, phospho-SMAD2/3, Akt and peroxisome proliferator activated receptor γ (PPARγ) were studied by western blot. Expression of the tight junction proteins, occludin and claudin-1, were assessed by Western blot. Colon proteasome activities (chymotrypsin-like and trypsin-like activities) were assessed.

RESULTS

TNBS-treated rats had a higher colon weight/length ratio compared to control rats (P < 0.01). Furthermore, fibrosis and inflammation scores were higher in TNBS-treated rats compared to control rats (P < 0.01 for both). Colonic production of TGF-β production tended to be higher in TNBS-treated rats (P < 0.06). Fibrosis-related proteins such as phospho-p38, phospho-SMAD2/3, and PPARγ were significantly higher in TNBS-treated rats compared to control rats (all P < 0.05). TNBS rats had a higher expression of Akt compared to control rats (P < 0.01). Tight junction proteins were modified by repeated TNBS challenge: colon occludin expression rose significantly (P < 0.01), whereas claudin-1 expression fell (P < 0.01). Bortezomib inhibition significantly decreased chymotrypsin-like activity (P < 0.05), but had no significant effect on trypsin-like activity (P > 0.05). In contrast, bortezomib had no effect on other studied parameters such as fibrosis score, TGF-β signaling, or tight junction expression (P > 0.05 for all).

CONCLUSION

Rats with TNBS-induced chronic colitis exhibited colon fibrosis associated with higher TGF-β signaling. Proteasome inhibition by bortezomib had no effect on fibrosis in our experimental conditions.

Authors+Show Affiliations

Emilien Loeuillard, Julien Bertrand, Anni Herranen, Chloé Melchior, Charlène Guérin, Moïse Coëffier, Pierre Déchelotte, Guillaume Savoye, Rachel Marion-Letellier, INSERM Unit UMR1073, Rouen University and Rouen University Hospital, Rouen Cedex 76183, France.Emilien Loeuillard, Julien Bertrand, Anni Herranen, Chloé Melchior, Charlène Guérin, Moïse Coëffier, Pierre Déchelotte, Guillaume Savoye, Rachel Marion-Letellier, INSERM Unit UMR1073, Rouen University and Rouen University Hospital, Rouen Cedex 76183, France.Emilien Loeuillard, Julien Bertrand, Anni Herranen, Chloé Melchior, Charlène Guérin, Moïse Coëffier, Pierre Déchelotte, Guillaume Savoye, Rachel Marion-Letellier, INSERM Unit UMR1073, Rouen University and Rouen University Hospital, Rouen Cedex 76183, France.Emilien Loeuillard, Julien Bertrand, Anni Herranen, Chloé Melchior, Charlène Guérin, Moïse Coëffier, Pierre Déchelotte, Guillaume Savoye, Rachel Marion-Letellier, INSERM Unit UMR1073, Rouen University and Rouen University Hospital, Rouen Cedex 76183, France.Emilien Loeuillard, Julien Bertrand, Anni Herranen, Chloé Melchior, Charlène Guérin, Moïse Coëffier, Pierre Déchelotte, Guillaume Savoye, Rachel Marion-Letellier, INSERM Unit UMR1073, Rouen University and Rouen University Hospital, Rouen Cedex 76183, France.Emilien Loeuillard, Julien Bertrand, Anni Herranen, Chloé Melchior, Charlène Guérin, Moïse Coëffier, Pierre Déchelotte, Guillaume Savoye, Rachel Marion-Letellier, INSERM Unit UMR1073, Rouen University and Rouen University Hospital, Rouen Cedex 76183, France.Emilien Loeuillard, Julien Bertrand, Anni Herranen, Chloé Melchior, Charlène Guérin, Moïse Coëffier, Pierre Déchelotte, Guillaume Savoye, Rachel Marion-Letellier, INSERM Unit UMR1073, Rouen University and Rouen University Hospital, Rouen Cedex 76183, France.Emilien Loeuillard, Julien Bertrand, Anni Herranen, Chloé Melchior, Charlène Guérin, Moïse Coëffier, Pierre Déchelotte, Guillaume Savoye, Rachel Marion-Letellier, INSERM Unit UMR1073, Rouen University and Rouen University Hospital, Rouen Cedex 76183, France.Emilien Loeuillard, Julien Bertrand, Anni Herranen, Chloé Melchior, Charlène Guérin, Moïse Coëffier, Pierre Déchelotte, Guillaume Savoye, Rachel Marion-Letellier, INSERM Unit UMR1073, Rouen University and Rouen University Hospital, Rouen Cedex 76183, France.Emilien Loeuillard, Julien Bertrand, Anni Herranen, Chloé Melchior, Charlène Guérin, Moïse Coëffier, Pierre Déchelotte, Guillaume Savoye, Rachel Marion-Letellier, INSERM Unit UMR1073, Rouen University and Rouen University Hospital, Rouen Cedex 76183, France.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25561788

Citation

Loeuillard, Emilien, et al. "2,4,6-trinitrobenzene Sulfonic Acid-induced Chronic Colitis With Fibrosis and Modulation of TGF-β1 Signaling." World Journal of Gastroenterology, vol. 20, no. 48, 2014, pp. 18207-15.
Loeuillard E, Bertrand J, Herranen A, et al. 2,4,6-trinitrobenzene sulfonic acid-induced chronic colitis with fibrosis and modulation of TGF-β1 signaling. World J Gastroenterol. 2014;20(48):18207-15.
Loeuillard, E., Bertrand, J., Herranen, A., Melchior, C., Guérin, C., Coëffier, M., ... Marion-Letellier, R. (2014). 2,4,6-trinitrobenzene sulfonic acid-induced chronic colitis with fibrosis and modulation of TGF-β1 signaling. World Journal of Gastroenterology, 20(48), pp. 18207-15. doi:10.3748/wjg.v20.i48.18207.
Loeuillard E, et al. 2,4,6-trinitrobenzene Sulfonic Acid-induced Chronic Colitis With Fibrosis and Modulation of TGF-β1 Signaling. World J Gastroenterol. 2014 Dec 28;20(48):18207-15. PubMed PMID: 25561788.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 2,4,6-trinitrobenzene sulfonic acid-induced chronic colitis with fibrosis and modulation of TGF-β1 signaling. AU - Loeuillard,Emilien, AU - Bertrand,Julien, AU - Herranen,Anni, AU - Melchior,Chloé, AU - Guérin,Charlène, AU - Coëffier,Moïse, AU - Aziz,Moutaz, AU - Déchelotte,Pierre, AU - Savoye,Guillaume, AU - Marion-Letellier,Rachel, PY - 2014/05/05/received PY - 2014/06/30/revised PY - 2014/09/05/accepted PY - 2015/1/7/entrez PY - 2015/1/7/pubmed PY - 2015/10/23/medline KW - Bortezomib KW - Colitis KW - Fibrosis KW - Proteasome SP - 18207 EP - 15 JF - World journal of gastroenterology JO - World J. Gastroenterol. VL - 20 IS - 48 N2 - AIM: To investigate whether targeting proteasome might reverse intestinal fibrosis in rats. METHODS: Chronic colitis was induced in rats by repeated administration of increasing dose of 2,4,6-trinitrobenzene sulfonic acid (TNBS, 15, 30, 45, 60, 60, 60 mg) by rectal injection for 6 wk (from day 0 to day 35), while control rats received the vehicle. TNBS + bortezomib (BTZ) rats received intraperitoneal injections of BTZ twice weekly (from day 37 to day 44) at a dose of 25 mg/kg, whereas the control and TNBS groups received the same amount of the vehicle. Histologic scoring of inflammation and fibrosis was performed. Colonic production of transforming growth factor (TGF)-β was measured by ELISA. Colon fibrosis-related proteins such as phospho-p38, phospho-SMAD2/3, Akt and peroxisome proliferator activated receptor γ (PPARγ) were studied by western blot. Expression of the tight junction proteins, occludin and claudin-1, were assessed by Western blot. Colon proteasome activities (chymotrypsin-like and trypsin-like activities) were assessed. RESULTS: TNBS-treated rats had a higher colon weight/length ratio compared to control rats (P < 0.01). Furthermore, fibrosis and inflammation scores were higher in TNBS-treated rats compared to control rats (P < 0.01 for both). Colonic production of TGF-β production tended to be higher in TNBS-treated rats (P < 0.06). Fibrosis-related proteins such as phospho-p38, phospho-SMAD2/3, and PPARγ were significantly higher in TNBS-treated rats compared to control rats (all P < 0.05). TNBS rats had a higher expression of Akt compared to control rats (P < 0.01). Tight junction proteins were modified by repeated TNBS challenge: colon occludin expression rose significantly (P < 0.01), whereas claudin-1 expression fell (P < 0.01). Bortezomib inhibition significantly decreased chymotrypsin-like activity (P < 0.05), but had no significant effect on trypsin-like activity (P > 0.05). In contrast, bortezomib had no effect on other studied parameters such as fibrosis score, TGF-β signaling, or tight junction expression (P > 0.05 for all). CONCLUSION: Rats with TNBS-induced chronic colitis exhibited colon fibrosis associated with higher TGF-β signaling. Proteasome inhibition by bortezomib had no effect on fibrosis in our experimental conditions. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/25561788/246_trinitrobenzene_sulfonic_acid_induced_chronic_colitis_with_fibrosis_and_modulation_of_TGF_β1_signaling_ L2 - http://www.wjgnet.com/1007-9327/full/v20/i48/18207.htm DB - PRIME DP - Unbound Medicine ER -