miR-194 Up-Regulates Cholesterol 7 Alpha-Hydroxylase Expression via β-Catenin Signaling and Aggravates Cholestatic Liver Diseases

Chen, Po-Chun; Hsu, Chien-Peng; Wang, Sheng-Ya; Wu, Tsai-Yen; Lin, Yu‐Jyun; Chen, You-Tzung; Hsu, Shu-Hao

doi:10.1016/j.ajpath.2023.02.007

Cited by 1 publication

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“…CTNNB1 encodes a protein that is part of a complex of proteins that make up adherens junctions (AJs) ( van der Wal and van Amerongen, 2020 ), which are essential for creating and maintaining epithelial cell layers by regulating cell growth and adhesion between cells. In addition, CTNNB1 is related to cholesterol homeostasis ( Chen et al, 2023 ), which might also be the mechanical basis of the association between plasma CTNNB1 level and AMD risk.…”

Section: Discussionmentioning

confidence: 99%

Identification of systemic biomarkers and potential drug targets for age-related macular degeneration

Lei,

Hu,

Wei

2024

Front. Aging Neurosci.

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PurposeSince age-related macular degeneration (AMD) is tightly associated with aging and cellular senescence, objective of this study was to investigate the association between plasma levels of senescence-related proteins (SRPs) and risk of AMD.DesignThe whole study was based on two-sample Mendelian randomization (MR) analysis.MethodsFor MR analysis, the primary approach for MR analysis was the inverse-variance weighted (IVW) method and the heterogeneity and pleiotropy of results were tested. The instrumental single-nucleotide polymorphisms (SNPs) associated with 110 SRPs were filtered and selected from a large genome-wide association study (GWAS) for plasma proteome involving 35,559 participants. The GWAS data of AMD was obtained from FinnGen consortium (6,157 AMD cases and 288,237 controls) and further validated by using data from UK Biobank consortium (3,553 AMD cases and 147,089 controls).ResultsThe MR results at both discovery and validation stages supported the causality (IVW-P < 0.00045) between plasma levels of 4 SRPs (C3b, CTNNB1, CCL1, and CCL3L1) and the risk of AMD and supported potential causality (IVW-P < 0.05) between other 10 SRPs and risk of AMD. No heterogeneity or pleiotropy in these results was detected.ConclusionOur findings supported that high plasma levels of C3b, CTNNB1, CCL1, and CCL3L1 were associated with increased risk of AMD, thereby highlighting the role of systemic inflammation in AMD pathogenesis and providing the rationale for developing new preventative and therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%