Evidence map›Paper›PMID 42323451›Full record

ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2026

Inhibition of IP6K1 suppresses NPA formation via platelet short-chain polyphosphate polymers in necrotizing enterocolitis.

Kai Gao, Muyang Zhu, Qianyang Liu, Yue Ma, Hongmei Xu, Chunbao Guo

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Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 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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5 · Who and what money

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6 authors.

Kai Gao *Department of Pediatrics, Chongqing Health Center for Women and Children, Women and Children's Hospital of Chongqing Medical University, 120 Longshan Rd, Chongqing, 401147, People's Republic of China.
Muyang Zhu *Department of Pediatrics, Chongqing Health Center for Women and Children, Women and Children's Hospital of Chongqing Medical University, 120 Longshan Rd, Chongqing, 401147, People's Republic of China.
Qianyang Liu *Department of Pediatrics, Chongqing Health Center for Women and Children, Women and Children's Hospital of Chongqing Medical University, 120 Longshan Rd, Chongqing, 401147, People's Republic of China.
Yue MaDepartment of Pediatrics, Chongqing Health Center for Women and Children, Women and Children's Hospital of Chongqing Medical University, 120 Longshan Rd, Chongqing, 401147, People's Republic of China.
Hongmei XuDepartment of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400010, People's Republic of China.
Chunbao GuoDepartment of Pediatrics, Chongqing Health Center for Women and Children, Women and Children's Hospital of Chongqing Medical University, 120 Longshan Rd, Chongqing, 401147, People's Republic of China. guochunbao@foxmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNecrotizing enterocolitis (NEC) is a life-threatening intestinal inflammatory disease in preterm infants. Inositol hexakisphosphate kinase 1 (IP6K1) regulates platelet polyphosphate (polyP) homeostasis, yet its roles in NEC remain unclear.

objectiveThis study aimed to investigate the regulatory mechanism of platelet IP6K1 in neutrophil-platelet aggregate (NPA) formation and NEC pathogenesis, and to evaluate the therapeutic potential of IP6K1 inhibition.

methodsClinical samples from patients with NEC were analyzed to assess circulating mitochondrial DNA, anticardiolipin IgG levels, platelet alterations, platelet cell death patterns, and NPA formation. A mouse model of NEC was used to evaluate the effects of genetic IP6K1 deficiency and pharmacological IP6K inhibition with TNP on survival, intestinal injury, neutrophil infiltration, neutrophil extracellular trap (NET) formation, and inflammatory responses. Mechanistic experiments were performed using exogenous polyP supplementation and P-selectin neutralization

resultsPatients with NEC exhibited significantly increased circulating mitochondrial DNA levels, elevated anticardiolipin IgG levels, enhanced NPA formation, reduced platelet counts, abnormal platelet morphological parameters, and platelet pyroptosis as the predominant mode of cell death. In NEC mice, both IP6K1 deficiency and TNP treatment improved survival, preserved intestinal mucosal architecture, reduced disease severity, and markedly attenuated neutrophil infiltration and NET formation. Mechanistically, IP6K1 promoted NPA formation and downstream inflammatory responses by regulating the release of platelet-derived short-chain polyP. Exogenous polyP supplementation restored the impaired NPA formation observed in IP6K1⁻/⁻ mice. Moreover, P-selectin neutralization suppressed NPA formation and reduced NET production in inflamed intestinal tissues.

conclusionPlatelet IP6K1 is a key regulator of NPA formation and NET release in NEC through its control of platelet-derived short-chain polyP. Targeting IP6K1 may represent a promising therapeutic strategy for mitigating local and systemic inflammation in severe NEC.

Indexed as

Blood PlateletsEnterocolitis, NecrotizingNeutrophilsPhosphotransferases (Phosphate Group Acceptor)PolyphosphatesAnimalsDNA, MitochondrialExtracellular TrapsFemaleHumansInfant, NewbornMaleMiceMice, Inbred C57BLPlatelet AggregationDNA, MitochondrialPhosphotransferases (Phosphate Group Acceptor)PolyphosphatesIP6K1Necrotizing enterocolitisNeutrophil extracellular trapsNeutrophil-platelet aggregatesPlateletsPolyphosphate

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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.