Evidence map›Paper›PMID 40937171›Full record

ArticleGastro hep advances2025

Beta-Klotho Protein Expression in Healthy Human Tissues and Liver Biopsies From Patients With MASLD or MASH.

Alexandra S Aaldijk, Dicky Struik, Stan Driessen, Cristy R C Verzijl, Joanne Verheij, Max Nieuwdorp, Roos Eilers, Justina C Wolters, Adriaan G Holleboom, Johan W Jonker

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Article in Gastro hep advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Alexandra S AaldijkDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Dicky StruikDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Stan DriessenDepartment of Vascular and Internal Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands.
Cristy R C VerzijlDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Joanne VerheijDepartment of Pathology, Amsterdam University Medical Center, Amsterdam, The Netherlands.
Max NieuwdorpDepartment of Vascular and Internal Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands.
Roos EilersDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Justina C WoltersDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Adriaan G HolleboomDepartment of Vascular and Internal Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands.
Johan W JonkerDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background and Aims: Biologics based on the structure of fibroblast growth factor (FGF) 19 and 21 show strong beneficial effects in the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD), including compensated cirrhosis. Studies in rodents indicated that the effectiveness of these drugs relies on the presence of transmembrane protein beta-klotho (KLB). However, the tissue expression profile of KLB and its regulation in liver disease remain poorly characterized. Here, we aim to investigate KLB protein expression in healthy human tissues and liver biopsies from patients with MASLD. Methods: Following extensive antibody validation, immunohistochemical analyses were conducted on paraffin-embedded human tissue samples to determine KLB protein tissue distribution. Subcellular localization of KLB was examined in cell lines expressing KLB either ectopically or endogenously. Additionally, KLB protein levels were quantified in 28 liver biopsies from patients with MASLD within the ANCHOR cohort study and correlated with histological MASLD features and clinical patient characteristics. Results: KLB protein expression was observed in the liver, bile ducts, gallbladder, stomach, colon, adipose tissue, and pancreas. Localization studies revealed that KLB was predominantly localized to the plasma membrane in both ectopic and endogenous contexts. KLB was also detected in liver biopsies from patients with MASLD/metabolic dysfunction-associated steatohepatitis and remained expressed at advanced stages of MASLD. Lower levels of hepatic KLB protein were significantly associated with higher levels of lobular inflammation ( Conclusion: This study provides insight into target organs for FGF-based drugs and demonstrates that hepatic KLB remains expressed throughout MASLD stages, supporting the use of FGF-based drugs in early and advanced stages of MASLD.

Indexed as

FGF19FGF21Hepatic SteatosisInflammationMASLD

Identifiers

PMID40937171
PMCPMC12421644

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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 OpenQuestion graph.