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Open AccessArticle

Transcriptional and Metabolomic Analysis of L-Arginine/Nitric Oxide Pathway in Inflammatory Bowel Disease and Its Association with Local Inflammatory and Angiogenic Response: Preliminary Findings

1
Department of Medical Biochemistry, Wroclaw Medical University, 50-368 Wrocław, Poland
2
Department of Gastroenterology and Hepatology, Wroclaw Medical University, 50-556 Wrocław, Poland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(5), 1641; https://doi.org/10.3390/ijms21051641
Received: 16 January 2020 / Revised: 25 February 2020 / Accepted: 26 February 2020 / Published: 28 February 2020
(This article belongs to the Special Issue Update on Basic and Molecular Research in Inflammatory Bowel Disease)
L-arginine/nitric oxide pathway in Crohn’s disease (CD) and ulcerative colitis (UC) is poorly investigated. The aim of current study is to quantify pathway serum metabolites in 52 CD (40 active), 48 UC (33 active), and 18 irritable bowel syndrome patients and 40 controls using mass spectrometry and at determining mRNA expression of pathway-associated enzymes in 91 bowel samples. Arginine and symmetric dimethylarginine decreased (p < 0.05) in active-CD (129 and 0.437 µM) compared to controls (157 and 0.494 µM) and active-UC (164 and 0.52 µM). Citrulline and dimethylamine increased (p < 0.05) in active-CD (68.7 and 70.9 µM) and active-UC (65.9 and 73.9 µM) compared to controls (42.7 and 50.4 µM). Compared to normal, CD-inflamed small bowel had downregulated (p < 0.05) arginase-2 by 2.4-fold and upregulated dimethylarginine dimethylaminohydrolase (DDAH)-2 (1.5-fold) and arginine N-methyltransferase (PRMT)-2 (1.6-fold). Quiescent-CD small bowel had upregulated (p < 0.05) arginase-2 (1.8-fold), DDAH1 (2.9-fold), DDAH2 (1.5-fold), PRMT1 (1.5-fold), PRMT2 (1.7-fold), and PRMT5 (1.4-fold). Pathway enzymes were upregulated in CD-inflamed/quiescent and UC-inflamed colon as compared to normal. Compared to inflamed, quiescent CD-colon had upregulated DDAH1 (5.7-fold) and ornithine decarboxylase (1.6-fold). Concluding, the pathway is deregulated in CD and UC, also in quiescent bowel, reflecting inflammation severity and angiogenic potential. Functional analysis of PRMTs and DDAHs as potential targets for therapy is warranted. View Full-Text
Keywords: Crohn’s disease; ulcerative colitis; arginase (ARG); nitric oxide synthase (NOS); arginine N-methyltransferase (PRMT); dimethylarginine dimethylaminohydrolase (DDAH); asymmetric dimethylarginine (ADMA); symmetric dimethylarginine (SDMA); L-citrulline; dimethylamine (DMA) Crohn’s disease; ulcerative colitis; arginase (ARG); nitric oxide synthase (NOS); arginine N-methyltransferase (PRMT); dimethylarginine dimethylaminohydrolase (DDAH); asymmetric dimethylarginine (ADMA); symmetric dimethylarginine (SDMA); L-citrulline; dimethylamine (DMA)
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MDPI and ACS Style

Krzystek-Korpacka, M.; G. Fleszar, M.; Bednarz-Misa, I.; Lewandowski, Ł.; Szczuka, I.; Kempiński, R.; Neubauer, K. Transcriptional and Metabolomic Analysis of L-Arginine/Nitric Oxide Pathway in Inflammatory Bowel Disease and Its Association with Local Inflammatory and Angiogenic Response: Preliminary Findings. Int. J. Mol. Sci. 2020, 21, 1641. https://doi.org/10.3390/ijms21051641

AMA Style

Krzystek-Korpacka M, G. Fleszar M, Bednarz-Misa I, Lewandowski Ł, Szczuka I, Kempiński R, Neubauer K. Transcriptional and Metabolomic Analysis of L-Arginine/Nitric Oxide Pathway in Inflammatory Bowel Disease and Its Association with Local Inflammatory and Angiogenic Response: Preliminary Findings. International Journal of Molecular Sciences. 2020; 21(5):1641. https://doi.org/10.3390/ijms21051641

Chicago/Turabian Style

Krzystek-Korpacka, Małgorzata; G. Fleszar, Mariusz; Bednarz-Misa, Iwona; Lewandowski, Łukasz; Szczuka, Izabela; Kempiński, Radosław; Neubauer, Katarzyna. 2020. "Transcriptional and Metabolomic Analysis of L-Arginine/Nitric Oxide Pathway in Inflammatory Bowel Disease and Its Association with Local Inflammatory and Angiogenic Response: Preliminary Findings" Int. J. Mol. Sci. 21, no. 5: 1641. https://doi.org/10.3390/ijms21051641

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