Ang1 and Ang4 differentially affect colitis and carcinogenesis in an AOM-DSS mouse model.
<h4>Introduction</h4>Angiogenin-1 (Ang1) and angiogenin-4 (Ang4) are 14-kDa ribonucleases with potent angiogenic and antimicrobial properties. The role of Ang1 and Ang4 in chronic colitis and colitis-associated cancer has not been previously studied.<h4>Methods</h4>Wild-type...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0281529 |
| _version_ | 1797843145570910208 |
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| author | Alexander Hu Cullen Roberts Andrei Moscalu Mark Redston James Yoo |
| author_facet | Alexander Hu Cullen Roberts Andrei Moscalu Mark Redston James Yoo |
| author_sort | Alexander Hu |
| collection | DOAJ |
| description | <h4>Introduction</h4>Angiogenin-1 (Ang1) and angiogenin-4 (Ang4) are 14-kDa ribonucleases with potent angiogenic and antimicrobial properties. The role of Ang1 and Ang4 in chronic colitis and colitis-associated cancer has not been previously studied.<h4>Methods</h4>Wild-type (WT) and angiogenin-1 knock-out (Ang1-KO) C57BL/6 mice were given azoxymethane, a colon carcinogen, 2 days in advance of three cycles of 3.5% dextran sodium sulfate (DSS). Disease activity index (DAI) was recorded, a colonoscopy was performed after each DSS treatment, and mice were euthanized (colitis, recovery, cancer) with tissue evaluated by histopathology. Ang1, Ang4, TNF-α, Il-1F062, IL-6, IL-10, IL-23, IL-33 mRNA levels were analyzed by RT-PCR.<h4>Results</h4>Ang1-KO mice exhibited more severe colitis compared to WT mice during both the acute (P<0.05) and recovery (P<0.05) phases of each DSS cycle. Consistent with these results, colonic TNF-α, IL1-β, IL-6, IL-10, and IL-33 mRNA levels were significantly upregulated in Ang1-KO mice (P<0.05). While Ang4 increased to similar levels in both WT and Ang1-KO mice during colitis and recovery phases, WT mice were distinguished by a significant upregulation of Ang1. Interestingly, despite the reduced colitis, WT mice developed significantly more tumors compared to Ang1-KO mice (P<0.05). 134 tumors formed in WT mice (4.6 tumors/mouse) while only 46 tumors formed (1.5 tumors/mice) in Ang1-KO mice, which were also characterized by a 34-fold decrease in Ang4 compared to WT mice and the complete absence of Ang1.<h4>Conclusions</h4>In a mouse model of colitis-associated cancer, Ang1-KO mice develop more severe colitis, but fewer tumors compared to WT mice. Ang1 levels correlate with the severity of colitis and the development of colitis-associated cancer, while Ang4 was upregulated during both colitis and cancer. Ang1 and Ang4 play important regulatory roles in the response to chronic colitis and the development of colitis-associated cancer and may serve as novel therapeutic targets. |
| first_indexed | 2024-04-09T17:00:04Z |
| format | Article |
| id | doaj.art-eb8c436a1250467aa3428a3237ef961a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-09T17:00:04Z |
| publishDate | 2023-01-01 |
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| spelling | doaj.art-eb8c436a1250467aa3428a3237ef961a2023-04-21T05:33:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01183e028152910.1371/journal.pone.0281529Ang1 and Ang4 differentially affect colitis and carcinogenesis in an AOM-DSS mouse model.Alexander HuCullen RobertsAndrei MoscaluMark RedstonJames Yoo<h4>Introduction</h4>Angiogenin-1 (Ang1) and angiogenin-4 (Ang4) are 14-kDa ribonucleases with potent angiogenic and antimicrobial properties. The role of Ang1 and Ang4 in chronic colitis and colitis-associated cancer has not been previously studied.<h4>Methods</h4>Wild-type (WT) and angiogenin-1 knock-out (Ang1-KO) C57BL/6 mice were given azoxymethane, a colon carcinogen, 2 days in advance of three cycles of 3.5% dextran sodium sulfate (DSS). Disease activity index (DAI) was recorded, a colonoscopy was performed after each DSS treatment, and mice were euthanized (colitis, recovery, cancer) with tissue evaluated by histopathology. Ang1, Ang4, TNF-α, Il-1F062, IL-6, IL-10, IL-23, IL-33 mRNA levels were analyzed by RT-PCR.<h4>Results</h4>Ang1-KO mice exhibited more severe colitis compared to WT mice during both the acute (P<0.05) and recovery (P<0.05) phases of each DSS cycle. Consistent with these results, colonic TNF-α, IL1-β, IL-6, IL-10, and IL-33 mRNA levels were significantly upregulated in Ang1-KO mice (P<0.05). While Ang4 increased to similar levels in both WT and Ang1-KO mice during colitis and recovery phases, WT mice were distinguished by a significant upregulation of Ang1. Interestingly, despite the reduced colitis, WT mice developed significantly more tumors compared to Ang1-KO mice (P<0.05). 134 tumors formed in WT mice (4.6 tumors/mouse) while only 46 tumors formed (1.5 tumors/mice) in Ang1-KO mice, which were also characterized by a 34-fold decrease in Ang4 compared to WT mice and the complete absence of Ang1.<h4>Conclusions</h4>In a mouse model of colitis-associated cancer, Ang1-KO mice develop more severe colitis, but fewer tumors compared to WT mice. Ang1 levels correlate with the severity of colitis and the development of colitis-associated cancer, while Ang4 was upregulated during both colitis and cancer. Ang1 and Ang4 play important regulatory roles in the response to chronic colitis and the development of colitis-associated cancer and may serve as novel therapeutic targets.https://doi.org/10.1371/journal.pone.0281529 |
| spellingShingle | Alexander Hu Cullen Roberts Andrei Moscalu Mark Redston James Yoo Ang1 and Ang4 differentially affect colitis and carcinogenesis in an AOM-DSS mouse model. PLoS ONE |
| title | Ang1 and Ang4 differentially affect colitis and carcinogenesis in an AOM-DSS mouse model. |
| title_full | Ang1 and Ang4 differentially affect colitis and carcinogenesis in an AOM-DSS mouse model. |
| title_fullStr | Ang1 and Ang4 differentially affect colitis and carcinogenesis in an AOM-DSS mouse model. |
| title_full_unstemmed | Ang1 and Ang4 differentially affect colitis and carcinogenesis in an AOM-DSS mouse model. |
| title_short | Ang1 and Ang4 differentially affect colitis and carcinogenesis in an AOM-DSS mouse model. |
| title_sort | ang1 and ang4 differentially affect colitis and carcinogenesis in an aom dss mouse model |
| url | https://doi.org/10.1371/journal.pone.0281529 |
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