Evidence map›Paper›PMID 41981505›Full record

ArticleBMC gastroenterology2026

Alkaline sphingomyelinase (ENPP7) attenuates DSS-induced colitis by modulating FOXO1-mediated antioxidative stress responses.

Wenting Cao, Yuqi Cheng, Xu Wang, Lingqi Wang, Rui Li, Siting Pei, Guihua Zhang, Jindong Ding Petersen, Ping Zhang

Abstract read
In one paragraph

Article in BMC gastroenterology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Wenting Cao *Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Academy of Medical Sciences, Hainan Medical University, No.3 Xueyuan Road, Haikou, Hainan Province, 571199, China.
Yuqi Cheng *Department of Clinical Laboratory, Anshan Hospital, First Affiliated Hospital of China Medical University, Anshan, Liaoning Province, 114039, China.
Xu Wang *Department of Laboratory Diagnosis, Qiqihar Tuberculosis Control Center, Qiqihar, Heilongjiang Province, 161000, China.
Lingqi WangDepartment of Laboratory Diagnosis, The Fifth Affiliated Hospital of Harbin Medical University, Daqing, Heilongjiang Province, 163319, China.
Rui LiKey Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Academy of Medical Sciences, Hainan Medical University, No.3 Xueyuan Road, Haikou, Hainan Province, 571199, China.
Siting PeiKey Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Academy of Medical Sciences, Hainan Medical University, No.3 Xueyuan Road, Haikou, Hainan Province, 571199, China.
Guihua ZhangDepartment of Clinical Laboratory, Anshan Hospital, First Affiliated Hospital of China Medical University, Anshan, Liaoning Province, 114039, China.
Jindong Ding PetersenKey Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Academy of Medical Sciences, Hainan Medical University, No.3 Xueyuan Road, Haikou, Hainan Province, 571199, China.
Ping ZhangKey Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Academy of Medical Sciences, Hainan Medical University, No.3 Xueyuan Road, Haikou, Hainan Province, 571199, China. pingxin2003@163.com.ORCID http://orcid.org/0000-0002-0987-4949

Funding

Natural Science Foundation of China 82560642Natural Science Foundation of Hainan Province 825RC774Talent Program of Hainan Medical University XRC2022007
6 · The paper itself

Abstract

backgroundAlkaline sphingomyelinase (alk-SMase), also known as ectonucleotide pyrophosphatase/phosphodiesterase 7 (ENPP7), is an intestinal enzyme involved in sphingolipid metabolism and has been implicated in the regulation of inflammation. However, its role in intestinal inflammation and the underlying mechanisms remain unclear. This study aimed to investigate the role of ENPP7 in dextran sulfate sodium (DSS)-induced colitis, with a particular focus on oxidative stress and FOXO1-related signaling pathways.

methodsENPP7 knockout (KO) and wild-type (WT) mice were used to establish a DSS-induced colitis model. Disease severity was assessed by body weight change, disease activity index (DAI), colon length, histopathological analysis, and plasma oxidative stress markers. Levels of pro-inflammatory cytokines and antioxidant enzymes were measured using standard biochemical assays. In vitro, polarized Caco-2 cells were subjected to ENPP7 knockdown and FOXO1 overexpression to evaluate their roles in antioxidative responses.

resultsENPP7 deficiency significantly aggravated DSS-induced colitis, as evidenced by greater body weight loss, higher DAI scores, and shorter colon length. This effect was accompanied by reduced FOXO1 expression, and was associated with diminished antioxidant defense and mitochondrial dysfunction-related alterations. Additionally, KO mice showed increased levels of pro-inflammatory cytokines (IL-1β and TNF-α) and decreased activities of antioxidant enzymes (CAT and SOD1) in intestinal mucosal tissues compared with WT mice. In Caco-2 cells, ENPP7 knockdown reduced FOXO1 expression, which was associated with impaired antioxidant capacity, whereas FOXO1 overexpression partially reversed these effects.

conclusionsENPP7 attenuates DSS-induced colitis, at least in part, by modulating FOXO1-mediated antioxidant responses, thereby influencing oxidative stress and inflammatory processes. These findings highlight ENPP7 as a potential therapeutic target for ulcerative colitis, although further mechanistic and clinical studies are warranted.

Indexed as

ColitisForkhead Box Protein O1Oxidative StressPhosphoric Diester HydrolasesSphingomyelin PhosphodiesteraseAnimalsCaco-2 CellsColonDextran SulfateDisease Models, AnimalHumansInterleukin-1betaMaleMiceMice, Inbred C57BLMice, KnockoutASMase, mouseDextran SulfateForkhead Box Protein O1Foxo1 protein, mouseInterleukin-1betaPhosphoric Diester HydrolasesSphingomyelin PhosphodiesteraseSuperoxide Dismutase-1Tumor Necrosis Factor-alphaAlkaline sphingomyelinase (ENPP7)Antioxidative stressDSS-induced colitisFOXO1

Identifiers

PMID41981505
PMCPMC13188645

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.