Adipokine C1q/Tumor Necrosis Factor- Related Protein 3 (CTRP3) Attenuates Intestinal Inflammation Via Sirtuin 1/NF-κB SignalingSummary
Background & Aims: The adipokine CTRP3 has anti-inflammatory effects in several nonintestinal disorders. Although serum CTRP3 is reduced in patients with inflammatory bowel disease (IBD), its function in IBD has not been established. Here, we elucidate the function of CTRP3 in intestinal inf...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X22002648 |
| _version_ | 1797867584433946624 |
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| author | Huimin Yu Zixin Zhang Gangping Li Yan Feng Lingling Xian Fatemeh Bakhsh Dongqing Xu Cheng Xu Tyrus Vong Bin Wu Florin M. Selaru Fengyi Wan Mark Donowitz G. William Wong |
| author_facet | Huimin Yu Zixin Zhang Gangping Li Yan Feng Lingling Xian Fatemeh Bakhsh Dongqing Xu Cheng Xu Tyrus Vong Bin Wu Florin M. Selaru Fengyi Wan Mark Donowitz G. William Wong |
| author_sort | Huimin Yu |
| collection | DOAJ |
| description | Background & Aims: The adipokine CTRP3 has anti-inflammatory effects in several nonintestinal disorders. Although serum CTRP3 is reduced in patients with inflammatory bowel disease (IBD), its function in IBD has not been established. Here, we elucidate the function of CTRP3 in intestinal inflammation. Methods: CTRP3 knockout (KO) and overexpressing transgenic (Tg) mice, along with their corresponding wild-type littermates, were treated with dextran sulfate sodium for 6–10 days. Colitis phenotypes and histologic data were analyzed. CTRP3-mediated signaling was examined in murine and human intestinal mucosa and mouse intestinal organoids derived from CTRP3 KO and Tg mice. Results: CTRP3 KO mice developed more severe colitis, whereas CTRP3 Tg mice developed less severe colitis than wild-type littermates. The deletion of CTRP3 correlated with decreased levels of Sirtuin-1 (SIRT1), a histone deacetylase, and increased levels of phosphorylated/acetylated NF-κB subunit p65 and proinflammatory cytokines tumor necrosis factor-α and interleukin-6. Results from CTRP3 Tg mice were inverse to those from CTRP3 KO mice. The addition of SIRT1 activator resveratrol to KO intestinal organoids and SIRT1 inhibitor Ex-527 to Tg intestinal organoids suggest that SIRT1 is a downstream effector of CTRP3-related inflammatory changes. In patients with IBD, a similar CTRP3/SIRT1/NF-κB relationship was observed. Conclusions: CTRP3 expression levels correlate negatively with intestinal inflammation in acute mouse colitis models and patients with IBD. CTRP3 may attenuate intestinal inflammation via SIRT1/NF-κB signaling. The manipulation of CTRP3 signaling, including through the use of SIRT1 activators, may offer translational potential in the treatment of IBD. |
| first_indexed | 2024-04-09T23:42:31Z |
| format | Article |
| id | doaj.art-387ac2fa670e4b77a63d9130180641ca |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-04-09T23:42:31Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-387ac2fa670e4b77a63d9130180641ca2023-03-18T04:42:07ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2023-01-0115410001015Adipokine C1q/Tumor Necrosis Factor- Related Protein 3 (CTRP3) Attenuates Intestinal Inflammation Via Sirtuin 1/NF-κB SignalingSummaryHuimin Yu0Zixin Zhang1Gangping Li2Yan Feng3Lingling Xian4Fatemeh Bakhsh5Dongqing Xu6Cheng Xu7Tyrus Vong8Bin Wu9Florin M. Selaru10Fengyi Wan11Mark Donowitz12G. William Wong13Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; Correspondence Address correspondence to: Huimin Yu, MD, PhD, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Research Building, Room 933, Baltimore, Maryland 21205.Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MarylandDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MarylandDepartment of Pathology and Laboratory Medicine, Pennsylvania Hospital, Penn Medicine, Philadelphia, PennsylvaniaDivision of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MarylandDepartment of Biophysics and Biophysics and Biochemistry, Johns Hopkins University School of Medicine, Baltimore, MarylandDepartment of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MarylandDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, MarylandDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MarylandDepartment of Biophysics and Biophysics and Biochemistry, Johns Hopkins University School of Medicine, Baltimore, MarylandDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MarylandDepartment of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MarylandDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MarylandDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, MarylandBackground & Aims: The adipokine CTRP3 has anti-inflammatory effects in several nonintestinal disorders. Although serum CTRP3 is reduced in patients with inflammatory bowel disease (IBD), its function in IBD has not been established. Here, we elucidate the function of CTRP3 in intestinal inflammation. Methods: CTRP3 knockout (KO) and overexpressing transgenic (Tg) mice, along with their corresponding wild-type littermates, were treated with dextran sulfate sodium for 6–10 days. Colitis phenotypes and histologic data were analyzed. CTRP3-mediated signaling was examined in murine and human intestinal mucosa and mouse intestinal organoids derived from CTRP3 KO and Tg mice. Results: CTRP3 KO mice developed more severe colitis, whereas CTRP3 Tg mice developed less severe colitis than wild-type littermates. The deletion of CTRP3 correlated with decreased levels of Sirtuin-1 (SIRT1), a histone deacetylase, and increased levels of phosphorylated/acetylated NF-κB subunit p65 and proinflammatory cytokines tumor necrosis factor-α and interleukin-6. Results from CTRP3 Tg mice were inverse to those from CTRP3 KO mice. The addition of SIRT1 activator resveratrol to KO intestinal organoids and SIRT1 inhibitor Ex-527 to Tg intestinal organoids suggest that SIRT1 is a downstream effector of CTRP3-related inflammatory changes. In patients with IBD, a similar CTRP3/SIRT1/NF-κB relationship was observed. Conclusions: CTRP3 expression levels correlate negatively with intestinal inflammation in acute mouse colitis models and patients with IBD. CTRP3 may attenuate intestinal inflammation via SIRT1/NF-κB signaling. The manipulation of CTRP3 signaling, including through the use of SIRT1 activators, may offer translational potential in the treatment of IBD.http://www.sciencedirect.com/science/article/pii/S2352345X22002648Adipokine CTRP3Intestinal InflammationIBDSIRT1/NF-κB SignalingIntestinal organoids |
| spellingShingle | Huimin Yu Zixin Zhang Gangping Li Yan Feng Lingling Xian Fatemeh Bakhsh Dongqing Xu Cheng Xu Tyrus Vong Bin Wu Florin M. Selaru Fengyi Wan Mark Donowitz G. William Wong Adipokine C1q/Tumor Necrosis Factor- Related Protein 3 (CTRP3) Attenuates Intestinal Inflammation Via Sirtuin 1/NF-κB SignalingSummary Cellular and Molecular Gastroenterology and Hepatology Adipokine CTRP3 Intestinal Inflammation IBD SIRT1/NF-κB Signaling Intestinal organoids |
| title | Adipokine C1q/Tumor Necrosis Factor- Related Protein 3 (CTRP3) Attenuates Intestinal Inflammation Via Sirtuin 1/NF-κB SignalingSummary |
| title_full | Adipokine C1q/Tumor Necrosis Factor- Related Protein 3 (CTRP3) Attenuates Intestinal Inflammation Via Sirtuin 1/NF-κB SignalingSummary |
| title_fullStr | Adipokine C1q/Tumor Necrosis Factor- Related Protein 3 (CTRP3) Attenuates Intestinal Inflammation Via Sirtuin 1/NF-κB SignalingSummary |
| title_full_unstemmed | Adipokine C1q/Tumor Necrosis Factor- Related Protein 3 (CTRP3) Attenuates Intestinal Inflammation Via Sirtuin 1/NF-κB SignalingSummary |
| title_short | Adipokine C1q/Tumor Necrosis Factor- Related Protein 3 (CTRP3) Attenuates Intestinal Inflammation Via Sirtuin 1/NF-κB SignalingSummary |
| title_sort | adipokine c1q tumor necrosis factor related protein 3 ctrp3 attenuates intestinal inflammation via sirtuin 1 nf κb signalingsummary |
| topic | Adipokine CTRP3 Intestinal Inflammation IBD SIRT1/NF-κB Signaling Intestinal organoids |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X22002648 |
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