Soluble Siglec-9 Improves Intestinal Barrier Function in a Mouse Model of Metabolic Dysfunction-Associated Steatohepatitis Article Swipe

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Hisanori Muto , Fumitaka Mizuno , Takashi Honda , Shinya Yokoyama , Taku Tanaka , Kenta Yamamoto , Takanori Ito , Norihiro Imai , Yoji Ishizu , Kiyoshi Sakai , Hideharu Hibi , Masatoshi Ishigami , Hiroki Kawashima ·

YOU? · · 2025 · Open Access · · DOI: https://doi.org/10.20944/preprints202504.1368.v1

Background/Objectives: Metabolic dysfunction-associated steatohepatitis (MASH), characterized by liver inflammation, fibrosis, and fat accumulation, can develop into cirrhosis and liver cancer. Despite its increasing prevalence worldwide, there are few established therapies for advanced MASH. We previously demonstrated that stem cells from human exfoliated deciduous teeth-conditioned media (SHED-CM) exerted therapeutic effects in a MASH mouse model. The gut-liver axis is thought to be associated with liver disease progression, and soluble Siglec-9 (sSiglec-9), an immunoinhibitory receptor, is a key protein in SHED-CM that induces anti-inflammatory macrophages and has intestinal epithelial protective effects. Therefore, we evaluated sSiglec-9’s role in intestinal barrier protection in MASH mice. Methods: We evaluated sSiglec-9 effects on intestinal barrier function using in vitro Caco-2 cell monolayers injured by TNF-α and IFN-γ. For the MASH mouse model, male C57BL/6J mice were given a Western diet and high-sugar solution orally; to induce liver injury, CCl4 was intraperitoneally administered for 12 weeks. Mice were treated weekly with 10 ng/g sSiglec-9 or vehicle. Intestinal permeability was assessed by blood 4 kDa FITC-dextran concentration, and intestinal transcriptomes and liver histology were analyzed. Results: sSiglec-9 decreased intestinal permeability and liver inflammation in MASH mice. sSiglec-9 and SHED-CM reduced 4 kDa FITC-dextran permeability in injured Caco-2 cells, and sSiglec-9 significantly reduced intestinal permeability and modulated expression of 34 intestinal genes. NAFLD Activity Score indicated significantly reduced inflammation following sSiglec-9 treatment. Conclusions: sSiglec-9 may protect intestinal barrier function by mitigating mucosal inflammation. sSiglec-9 treatment may represent a novel therapeutic approach for MASH via gut-liver axis modulation.

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Steatohepatitis Function (biology) SIGLEC Medicine Biology Internal medicine Cell biology Fatty liver Disease Receptor

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Type: preprint
Language: en
Landing Page: https://doi.org/10.20944/preprints202504.1368.v1
PDF: https://www.preprints.org/frontend/manuscript/4d8ee2b8db80078e0abff96ff742dd38/download_pub
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OpenAlex ID: https://openalex.org/W4409587889

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DOI: https://doi.org/10.20944/preprints202504.1368.v1

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Title: Soluble Siglec-9 Improves Intestinal Barrier Function in a Mouse Model of Metabolic Dysfunction-Associated Steatohepatitis

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Type: preprint

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Language: en

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Publication year: 2025

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Publication date: 2025-04-16

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Authors: Hisanori Muto, Fumitaka Mizuno, Takashi Honda, Shinya Yokoyama, Taku Tanaka, Kenta Yamamoto, Takanori Ito, Norihiro Imai, Yoji Ishizu, Kiyoshi Sakai, Hideharu Hibi, Masatoshi Ishigami, Hiroki Kawashima

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Landing page: https://doi.org/10.20944/preprints202504.1368.v1

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PDF URL: https://www.preprints.org/frontend/manuscript/4d8ee2b8db80078e0abff96ff742dd38/download_pub

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Concepts: Steatohepatitis, Function (biology), SIGLEC, Medicine, Biology, Internal medicine, Cell biology, Fatty liver, Disease, Receptor

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abstract_inverted_index.sSiglec-9	104, 156, 178, 188, 201, 221, 224, 234
abstract_inverted_index.therapies	29
abstract_inverted_index.treatment	235
abstract_inverted_index.Intestinal	159
abstract_inverted_index.Therefore,	89
abstract_inverted_index.associated	61
abstract_inverted_index.epithelial	86
abstract_inverted_index.exfoliated	41
abstract_inverted_index.expression	208
abstract_inverted_index.high-sugar	135
abstract_inverted_index.increasing	22
abstract_inverted_index.intestinal	85, 95, 107, 170, 180, 204, 211, 227
abstract_inverted_index.mitigating	231
abstract_inverted_index.monolayers	115
abstract_inverted_index.prevalence	23
abstract_inverted_index.previously	34
abstract_inverted_index.protection	97
abstract_inverted_index.protective	87
abstract_inverted_index.treatment.	222
abstract_inverted_index.worldwide,	24
abstract_inverted_index.established	28
abstract_inverted_index.macrophages	82
abstract_inverted_index.modulation.	247
abstract_inverted_index.therapeutic	47, 240
abstract_inverted_index.(sSiglec-9),	69
abstract_inverted_index.Conclusions:	223
abstract_inverted_index.FITC-dextran	167, 194
abstract_inverted_index.administered	145
abstract_inverted_index.demonstrated	35
abstract_inverted_index.inflammation	184, 219
abstract_inverted_index.permeability	160, 181, 195, 205
abstract_inverted_index.progression,	65
abstract_inverted_index.accumulation,	12
abstract_inverted_index.characterized	5
abstract_inverted_index.inflammation,	8
abstract_inverted_index.inflammation.	233
abstract_inverted_index.sSiglec-9’s	92
abstract_inverted_index.significantly	202, 217
abstract_inverted_index.concentration,	168
abstract_inverted_index.transcriptomes	171
abstract_inverted_index.steatohepatitis	3
abstract_inverted_index.immunoinhibitory	71
abstract_inverted_index.anti-inflammatory	81
abstract_inverted_index.intraperitoneally	144
abstract_inverted_index.teeth-conditioned	43
abstract_inverted_index.Background/Objectives:	0
abstract_inverted_index.dysfunction-associated	2
cited_by_percentile_year
countries_distinct_count	0
institutions_distinct_count	13
citation_normalized_percentile.value	0.18343678
citation_normalized_percentile.is_in_top_1_percent	False
citation_normalized_percentile.is_in_top_10_percent	False