Evaluation of microRNA-29a expression and Dipeptidyl-peptidase 4 level in ulcerative colitis patients
-
Golnaz Goodarzi
,
Sadra Samavarchi Tehrani
,
Saeed Ebrahimi Fana
,
Nafiseh Saleknezhad
,
Ghodratollah Panahi
,
Maryam Rayatpisheh
,
Amir Anushiravani
Abstract
Objective: Ulcerative colitis (UC) is a recurrent inflammatory bowel disease (IBD) that increases at an alarming rate around the world. The microRNA-29 (miRNA-29) family has been implicated in the pathogenesis of UC. In recent year, the alteration of Dipeptidyl-peptidase 4 (DPP4) levels in IBD patients has been reported. In the present study, we evaluated the relationship between miRNA-29a expression of intestinal tissue and serum DPP4 level in UC patients and healthy subjects.
Methods: Blood samples and colonic punch biopsy were obtained from 35 UC, and 29 healthy subjects. Serum levels of DPP-4 were evaluated by ELISA technique. The expression levels of miRNA-29 were assessed by qRT-PCR. Also, biochemical parameters and demographic information were collected based on patient tests and questionnaire.
Results: The results of this study showed a significant increase of miRNA-29a in intestinal tissue of UC patients compared to control. In addition, elevated expression of miRNA-29a was accompanied by a decrease in serum levels of DPP4, but there was no significant difference between moderate and severe conditions. Furthermore, the levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and platelet were higher in UC patients relative to those without UC.
Conclusions: These findings supported the role of the miRNA-29a-DPP4 axis in the pathogenesis of UC and provide the evidence for the further evaluation of this axis as biomarkers of the disease.
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3. Camarillo GF, Goyon EI, Zuñiga RB, Salas LAS, Escárcega AEP, Yamamoto-Furusho JK. Gene expression profiling of mediators associated with the inflammatory pathways in the intestinal tissue from patients with ulcerative colitis. Mediators of inflammation. 2020;2020.
4. Goodarzi G, Maniati M, Qujeq D. The role of microRNAs in the healing of diabetic ulcers. International wound journal. 2019;16(3):621-33.
5. Wu F, Zikusoka M, Trindade A, Dassopoulos T, Harris ML, Bayless TM, et al. MicroRNAs are differentially expressed in ulcerative colitis and alter expression of macrophage inflammatory peptide-2α. Gastroenterology. 2008;135(5):1624-35. e24.
6. Béres NJ, Szabó D, Kocsis D, Szűcs D, Kiss Z, Müller KE, et al. Role of altered expression of miR-146a, miR-155, and miR-122 in pediatric patients with inflammatory bowel disease. Inflammatory bowel diseases. 2016;22(2):327-35.
7. Schönauen K, Le N, von Arnim U, Schulz C, Malfertheiner P, Link A. Circulating and fecal microRNAs as biomarkers for inflammatory bowel diseases. Inflammatory bowel diseases. 2018;24(7):1547-57.
8. Valmiki S, Ahuja V, Paul J. MicroRNA exhibit altered expression in the inflamed colonic mucosa of ulcerative colitis patients. World journal of gastroenterology. 2017;23(29):5324.
9. James JP, Riis LB, Malham M, Høgdall E, Langholz E, Nielsen BS. MicroRNA biomarkers in IBD—Differential diagnosis and prediction of Colitis-Associated cancer. International Journal of Molecular Sciences. 2020;21(21):7893.
10. Shi C, Liang Y, Yang J, Xia Y, Chen H, Han H, et al. MicroRNA-21 knockout improve the survival rate in DSS induced fatal colitis through protecting against inflammation and tissue injury. PloS one. 2013;8(6):e66814.
11. Zhang L, Shen J, Cheng J, Fan X. MicroRNA‐21 regulates intestinal epithelial tight junction permeability. Cell biochemistry and function. 2015;33(4):235-40.
12. Horita M, Farquharson C, Stephen LA. The role of miR‐29 family in disease. Journal of cellular biochemistry. 2021;122(7):696-715.
13. Lv B, Liu Z, Wang S, Liu F, Yang X, Hou J, et al. MiR-29a promotes intestinal epithelial apoptosis in ulcerative colitis by down-regulating Mcl-1. International journal of clinical and experimental pathology. 2014;7(12):8542.
14. Biancheri P, Nijhuis A, Di Sabatino A, Lai C, Ghosh A, MacDonald T, et al. P057 Micro-RNA expression profiling identifies miR-29b as a relevant pro-fibrogenic factor in Crohn's disease intestinal strictures. Journal of Crohn's and Colitis. 2013;7(Supplement_1):S32-S.
15. Zhang J, Chen Q, Zhong J, Liu C, Zheng B, Gong Q. DPP-4 inhibitors as potential candidates for antihypertensive therapy: improving vascular inflammation and assisting the action of traditional antihypertensive drugs. Frontiers in immunology. 2019;10:1050.
16. Trzaskalski NA, Fadzeyeva E, Mulvihill EE. Dipeptidyl peptidase-4 at the interface between inflammation and metabolism. Clinical Medicine Insights: Endocrinology and Diabetes. 2020;13:1179551420912972.
17. Klemann C, Wagner L, Stephan M, von Hörsten S. Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system. Clinical & Experimental Immunology. 2016;185(1):1-21.
18. Radel JA, Pender DN, Shah SA. Dipeptidyl peptidase-4 inhibitors and inflammatory bowel disease risk: a meta-analysis. Annals of Pharmacotherapy. 2019;53(7):697-704.
19. Moran G, O'Neill C, Padfield P, McLaughlin J. Dipeptidyl peptidase-4 expression is reduced in Crohn's disease. Regulatory peptides. 2012;177(1-3):40-5.
20. Wang Y, Han J, Lv Y, Zhang G. miR-29a inhibits proliferation, invasion, and migration of papillary thyroid cancer by targeting DPP4. OncoTargets and therapy. 2019;12:4225.
21. Suri K, Bubier JA, Wiles MV, Shultz LD, Amiji MM, Hosur V. Role of microRNA in inflammatory bowel disease: Clinical evidence and the development of preclinical animal models. Cells. 2021;10(9):2204.
22. Tehrani SS, Zaboli E, Sadeghi F, Khafri S, Karimian A, Rafie M, et al. MicroRNA-26a-5p as a potential predictive factor for determining the effectiveness of trastuzumab therapy in HER-2 positive breast cancer patients. BioMedicine. 2021;11(2):30.
23. Li X, Sun L, Chen L, Xu Y, Kong X. Upregulation of microRNA-219-5p relieves ulcerative colitis through balancing the differentiation of Treg/Th17 cells. European Journal of Gastroenterology & Hepatology. 2020;32(7):813.
24. Xu Y, Yang J, Chen X, Deng J, Gong H, Li F, et al. MicroRNA-182-5p aggravates ulcerative colitis by inactivating the Wnt/β-catenin signaling pathway through DNMT3A-mediated SMARCA5 methylation. Genomics. 2022:110360.
25. Pinto-Lopes P, Afonso J, Pinto-Lopes R, Rocha C, Lago P, Gonçalves R, et al. Serum dipeptidyl peptidase 4: a predictor of disease activity and prognosis in inflammatory bowel disease. Inflammatory Bowel Diseases. 2020;26(11):1707-19.
26. Ning M-m, Yang W-j, Guan W-b, Gu Y-p, Feng Y, Leng Y. Dipeptidyl peptidase 4 inhibitor sitagliptin protected against dextran sulfate sodium-induced experimental colitis by potentiating the action of GLP-2. Acta Pharmacologica Sinica. 2020;41(11):1446-56.
27. Atanassova A, Teneva M. At the border of inflammation and fibrosis-serum expression of miR 29 in patients with inflammatory bowel disease. Journal of the Union of Scientists-Varna Medicine and Ecology Series. 2020;25(1).
28. Zhou Q, Costinean S, Croce CM, Brasier AR, Merwat S, Larson SA, et al. MicroRNA 29 targets nuclear factor-κB–repressing factor and Claudin 1 to increase intestinal permeability. Gastroenterology. 2015;148(1):158-69. e8.
29. Fasseu M, Tréton X, Guichard C, Pedruzzi E, Cazals-Hatem D, Richard C, et al. Identification of restricted subsets of mature microRNA abnormally expressed in inactive colonic mucosa of patients with inflammatory bowel disease. PloS one. 2010;5(10):e13160.
30. Niemiec SM, Louiselle AE, Liechty KW, Zgheib C. Role of microRNAs in pressure ulcer immune response, pathogenesis, and treatment. International Journal of Molecular Sciences. 2020;22(1):64.
31. Brain O, Owens BM, Pichulik T, Allan P, Khatamzas E, Leslie A, et al. The intracellular sensor NOD2 induces microRNA-29 expression in human dendritic cells to limit IL-23 release. Immunity. 2013;39(3):521-36.
32. Steiner DF, Thomas MF, Hu JK, Yang Z, Babiarz JE, Allen CD, et al. MicroRNA-29 regulates T-box transcription factors and interferon-γ production in helper T cells. Immunity. 2011;35(2):169-81.
33. Jaenisch SE, Abbott CA, Gorrell MD, Bampton P, Butler RN, Yazbeck R. Circulating Dipeptidyl Peptidase Activity Is a Potential Biomarker for Inflammatory Bowel Disease. Clinical and translational gastroenterology. 2022;13(1).
34. Hildebrandt M, Rose M, Rüter J, Salama A, Mönnikes H, Klapp B. Dipeptidyl peptidase IV (DP IV, CD26) in patients with inflammatory bowel disease. Scandinavian journal of gastroenterology. 2001;36(10):1067-72.
35. Magro DO, Kotze PG, Martinez CAR, Camargo MG, Guadagnini D, Calixto AR, et al. Changes in serum levels of lipopolysaccharides and CD26 in patients with Crohn's disease. Intestinal research. 2017;15(3):352.
36. Varljen J, Mijandrušić Sinčić B, Batičić L, Varljen N, Detel D, Lekić A. Clinical relevance of the serum dipeptidyl peptidase IV (DPP IV/CD26) activity in adult patients with Crohn’s disease and ulcerative colitis. Croatica Chemica Acta. 2005;78(3):427-32.
37. Cioffi M, De Rosa A, Serao R, Picone I, Vietri MT. Laboratory markers in ulcerative colitis: Current insights and future advances. World journal of gastrointestinal pathophysiology. 2015;6(1):13.
38. Rodgers AD, Cummins AG. CRP correlates with clinical score in ulcerative colitis but not in Crohn’s disease. Digestive diseases and sciences. 2007;52(9):2063-8.
39. Srivastava SP, Shi S, Kanasaki M, Nagai T, Kitada M, He J, et al. Effect of antifibrotic microRNAs crosstalk on the action of N-acetyl-seryl-aspartyl-lysyl-proline in diabetes-related kidney fibrosis. Scientific reports. 2016;6(1):1-12.
40. Xu M, Tian G, Hao C, Shi M, Zha D, Liang K. Microrna-29 targets FGF2 and inhibits the proliferation, migration and invasion of nasopharyngeal carcinoma cells via Pi3k/Akt signaling pathway. European Review for Medical and Pharmacological Sciences. 2019;23(12):5215-22.
41. Jash K, Gondaliya P, Sunkaria A, Kalia K. MicroRNA-29b Modulates β-Secretase Activity in SH-SY5Y Cell Line and Diabetic Mouse Brain. Cellular and Molecular Neurobiology. 2020;40(8):1367-81.
2. Du L, Ha C. Epidemiology and pathogenesis of ulcerative colitis. Gastroenterology Clinics. 2020;49(4):643-54.
3. Camarillo GF, Goyon EI, Zuñiga RB, Salas LAS, Escárcega AEP, Yamamoto-Furusho JK. Gene expression profiling of mediators associated with the inflammatory pathways in the intestinal tissue from patients with ulcerative colitis. Mediators of inflammation. 2020;2020.
4. Goodarzi G, Maniati M, Qujeq D. The role of microRNAs in the healing of diabetic ulcers. International wound journal. 2019;16(3):621-33.
5. Wu F, Zikusoka M, Trindade A, Dassopoulos T, Harris ML, Bayless TM, et al. MicroRNAs are differentially expressed in ulcerative colitis and alter expression of macrophage inflammatory peptide-2α. Gastroenterology. 2008;135(5):1624-35. e24.
6. Béres NJ, Szabó D, Kocsis D, Szűcs D, Kiss Z, Müller KE, et al. Role of altered expression of miR-146a, miR-155, and miR-122 in pediatric patients with inflammatory bowel disease. Inflammatory bowel diseases. 2016;22(2):327-35.
7. Schönauen K, Le N, von Arnim U, Schulz C, Malfertheiner P, Link A. Circulating and fecal microRNAs as biomarkers for inflammatory bowel diseases. Inflammatory bowel diseases. 2018;24(7):1547-57.
8. Valmiki S, Ahuja V, Paul J. MicroRNA exhibit altered expression in the inflamed colonic mucosa of ulcerative colitis patients. World journal of gastroenterology. 2017;23(29):5324.
9. James JP, Riis LB, Malham M, Høgdall E, Langholz E, Nielsen BS. MicroRNA biomarkers in IBD—Differential diagnosis and prediction of Colitis-Associated cancer. International Journal of Molecular Sciences. 2020;21(21):7893.
10. Shi C, Liang Y, Yang J, Xia Y, Chen H, Han H, et al. MicroRNA-21 knockout improve the survival rate in DSS induced fatal colitis through protecting against inflammation and tissue injury. PloS one. 2013;8(6):e66814.
11. Zhang L, Shen J, Cheng J, Fan X. MicroRNA‐21 regulates intestinal epithelial tight junction permeability. Cell biochemistry and function. 2015;33(4):235-40.
12. Horita M, Farquharson C, Stephen LA. The role of miR‐29 family in disease. Journal of cellular biochemistry. 2021;122(7):696-715.
13. Lv B, Liu Z, Wang S, Liu F, Yang X, Hou J, et al. MiR-29a promotes intestinal epithelial apoptosis in ulcerative colitis by down-regulating Mcl-1. International journal of clinical and experimental pathology. 2014;7(12):8542.
14. Biancheri P, Nijhuis A, Di Sabatino A, Lai C, Ghosh A, MacDonald T, et al. P057 Micro-RNA expression profiling identifies miR-29b as a relevant pro-fibrogenic factor in Crohn's disease intestinal strictures. Journal of Crohn's and Colitis. 2013;7(Supplement_1):S32-S.
15. Zhang J, Chen Q, Zhong J, Liu C, Zheng B, Gong Q. DPP-4 inhibitors as potential candidates for antihypertensive therapy: improving vascular inflammation and assisting the action of traditional antihypertensive drugs. Frontiers in immunology. 2019;10:1050.
16. Trzaskalski NA, Fadzeyeva E, Mulvihill EE. Dipeptidyl peptidase-4 at the interface between inflammation and metabolism. Clinical Medicine Insights: Endocrinology and Diabetes. 2020;13:1179551420912972.
17. Klemann C, Wagner L, Stephan M, von Hörsten S. Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system. Clinical & Experimental Immunology. 2016;185(1):1-21.
18. Radel JA, Pender DN, Shah SA. Dipeptidyl peptidase-4 inhibitors and inflammatory bowel disease risk: a meta-analysis. Annals of Pharmacotherapy. 2019;53(7):697-704.
19. Moran G, O'Neill C, Padfield P, McLaughlin J. Dipeptidyl peptidase-4 expression is reduced in Crohn's disease. Regulatory peptides. 2012;177(1-3):40-5.
20. Wang Y, Han J, Lv Y, Zhang G. miR-29a inhibits proliferation, invasion, and migration of papillary thyroid cancer by targeting DPP4. OncoTargets and therapy. 2019;12:4225.
21. Suri K, Bubier JA, Wiles MV, Shultz LD, Amiji MM, Hosur V. Role of microRNA in inflammatory bowel disease: Clinical evidence and the development of preclinical animal models. Cells. 2021;10(9):2204.
22. Tehrani SS, Zaboli E, Sadeghi F, Khafri S, Karimian A, Rafie M, et al. MicroRNA-26a-5p as a potential predictive factor for determining the effectiveness of trastuzumab therapy in HER-2 positive breast cancer patients. BioMedicine. 2021;11(2):30.
23. Li X, Sun L, Chen L, Xu Y, Kong X. Upregulation of microRNA-219-5p relieves ulcerative colitis through balancing the differentiation of Treg/Th17 cells. European Journal of Gastroenterology & Hepatology. 2020;32(7):813.
24. Xu Y, Yang J, Chen X, Deng J, Gong H, Li F, et al. MicroRNA-182-5p aggravates ulcerative colitis by inactivating the Wnt/β-catenin signaling pathway through DNMT3A-mediated SMARCA5 methylation. Genomics. 2022:110360.
25. Pinto-Lopes P, Afonso J, Pinto-Lopes R, Rocha C, Lago P, Gonçalves R, et al. Serum dipeptidyl peptidase 4: a predictor of disease activity and prognosis in inflammatory bowel disease. Inflammatory Bowel Diseases. 2020;26(11):1707-19.
26. Ning M-m, Yang W-j, Guan W-b, Gu Y-p, Feng Y, Leng Y. Dipeptidyl peptidase 4 inhibitor sitagliptin protected against dextran sulfate sodium-induced experimental colitis by potentiating the action of GLP-2. Acta Pharmacologica Sinica. 2020;41(11):1446-56.
27. Atanassova A, Teneva M. At the border of inflammation and fibrosis-serum expression of miR 29 in patients with inflammatory bowel disease. Journal of the Union of Scientists-Varna Medicine and Ecology Series. 2020;25(1).
28. Zhou Q, Costinean S, Croce CM, Brasier AR, Merwat S, Larson SA, et al. MicroRNA 29 targets nuclear factor-κB–repressing factor and Claudin 1 to increase intestinal permeability. Gastroenterology. 2015;148(1):158-69. e8.
29. Fasseu M, Tréton X, Guichard C, Pedruzzi E, Cazals-Hatem D, Richard C, et al. Identification of restricted subsets of mature microRNA abnormally expressed in inactive colonic mucosa of patients with inflammatory bowel disease. PloS one. 2010;5(10):e13160.
30. Niemiec SM, Louiselle AE, Liechty KW, Zgheib C. Role of microRNAs in pressure ulcer immune response, pathogenesis, and treatment. International Journal of Molecular Sciences. 2020;22(1):64.
31. Brain O, Owens BM, Pichulik T, Allan P, Khatamzas E, Leslie A, et al. The intracellular sensor NOD2 induces microRNA-29 expression in human dendritic cells to limit IL-23 release. Immunity. 2013;39(3):521-36.
32. Steiner DF, Thomas MF, Hu JK, Yang Z, Babiarz JE, Allen CD, et al. MicroRNA-29 regulates T-box transcription factors and interferon-γ production in helper T cells. Immunity. 2011;35(2):169-81.
33. Jaenisch SE, Abbott CA, Gorrell MD, Bampton P, Butler RN, Yazbeck R. Circulating Dipeptidyl Peptidase Activity Is a Potential Biomarker for Inflammatory Bowel Disease. Clinical and translational gastroenterology. 2022;13(1).
34. Hildebrandt M, Rose M, Rüter J, Salama A, Mönnikes H, Klapp B. Dipeptidyl peptidase IV (DP IV, CD26) in patients with inflammatory bowel disease. Scandinavian journal of gastroenterology. 2001;36(10):1067-72.
35. Magro DO, Kotze PG, Martinez CAR, Camargo MG, Guadagnini D, Calixto AR, et al. Changes in serum levels of lipopolysaccharides and CD26 in patients with Crohn's disease. Intestinal research. 2017;15(3):352.
36. Varljen J, Mijandrušić Sinčić B, Batičić L, Varljen N, Detel D, Lekić A. Clinical relevance of the serum dipeptidyl peptidase IV (DPP IV/CD26) activity in adult patients with Crohn’s disease and ulcerative colitis. Croatica Chemica Acta. 2005;78(3):427-32.
37. Cioffi M, De Rosa A, Serao R, Picone I, Vietri MT. Laboratory markers in ulcerative colitis: Current insights and future advances. World journal of gastrointestinal pathophysiology. 2015;6(1):13.
38. Rodgers AD, Cummins AG. CRP correlates with clinical score in ulcerative colitis but not in Crohn’s disease. Digestive diseases and sciences. 2007;52(9):2063-8.
39. Srivastava SP, Shi S, Kanasaki M, Nagai T, Kitada M, He J, et al. Effect of antifibrotic microRNAs crosstalk on the action of N-acetyl-seryl-aspartyl-lysyl-proline in diabetes-related kidney fibrosis. Scientific reports. 2016;6(1):1-12.
40. Xu M, Tian G, Hao C, Shi M, Zha D, Liang K. Microrna-29 targets FGF2 and inhibits the proliferation, migration and invasion of nasopharyngeal carcinoma cells via Pi3k/Akt signaling pathway. European Review for Medical and Pharmacological Sciences. 2019;23(12):5215-22.
41. Jash K, Gondaliya P, Sunkaria A, Kalia K. MicroRNA-29b Modulates β-Secretase Activity in SH-SY5Y Cell Line and Diabetic Mouse Brain. Cellular and Molecular Neurobiology. 2020;40(8):1367-81.
| Files | ||
| Issue | Vol 2 No 3 (2024) | |
| Section | Original Articles | |
| Keywords | ||
| Inflammatory Bowl Diseases Ulcerative colitis Dipeptidyl-peptidase 4 miRNA-29a Inflammation | ||
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How to Cite
1.
Goodarzi G, Samavarchi Tehrani S, Ebrahimi Fana S, Saleknezhad N, Panahi G, Rayatpisheh M, Anushiravani A. Evaluation of microRNA-29a expression and Dipeptidyl-peptidase 4 level in ulcerative colitis patients. ABI. 2024;2(3):162-169.
