Leucine-rich alpha-2-glycoprotein 1 deficiency suppresses ischemia–reperfusion injury-induced renal fibrosis

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 8, 2025

Ischemia reperfusion injury (IRI) is a major cause of acute kidney (AKI) and ultimately leads to renal fibrosis, primarily via the transforming growth factor-β (TGF-β) pathway. Leucine-rich alpha-2-glycoprotein 1 (LRG1), novel modulator TGF-β pathway, has been implicated in modulation fibrosis by affecting TGF-β/Smad3 signaling axis. However, role LRG1 transition from AKI chronic disease (CKD) remains unclear. This study aimed investigate functional during remodeling phase post-IRI. Unilateral IRI was induced C57BL/6J wild-type (WT) mice systemic knockout (KO) mice. In WT mice, mRNA expression significantly elevated on ischemia/reperfusion side compared sham over 28-day period. contrast, KO demonstrated reduced postoperative day 28. Additionally, associated pro-fibrotic genes diminished Consequently, exhibited attenuated IRI-induced fibrosis. These findings indicate that involved pathogenesis CKD may be potential therapeutic target.

Язык: Английский

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Identification of a multi-omics factor predictive of long COVID in the IMPACC study

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 14, 2025

Following SARS-CoV-2 infection, ∼10-35% of COVID-19 patients experience long COVID (LC), in which often debilitating symptoms persist for at least three months. Elucidating the biologic underpinnings LC could identify therapeutic opportunities. We utilized machine learning methods on analytes and patient reported outcome surveys provided over 12 months after hospital discharge from >500 hospitalized IMPACC cohort to a multi-omics "recovery factor". participants who experienced had lower recovery factor scores compared without LC. Biologic characterization revealed increased levels plasma proteins associated with inflammation, elevated transcriptional signatures heme metabolism, decreased androgenic steroids patients. The was also altered circulating immune cell frequencies. Notably, were predictive occurrence as early admission, irrespective acute disease severity. Thus, identifies risk infection reveals biomarkers potential treatment targets.

Язык: Английский

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LRG1 Alters Pericyte Phenotype and Compromises Vascular Maturation

Cells, Год журнала: 2025, Номер 14(8), С. 593 - 593

Опубликована: Апрель 14, 2025

Upregulation of leucine-rich alpha-2-glycoprotein-1 (LRG1) contributes to aberrant neovascularization in many different diseases. In contrast, LRG1 is not involved developmental angiogenesis. Here, we investigated the vasculopathic properties by examining its effect on developing retinal blood vessels. By injecting recombinant protein or an expression vector into mouse retina during vascular development, showed that exogenous reduces pericyte coverage and NG2 expression. It leads diminished collagen IV sheathing, fewer adhesion gap junctions, reduced vessel calibre density. Moreover, retinae containing LRG1, blood–retinal barrier remains more permeable with significantly higher numbers transcytotic vesicles present microvascular endothelial cells. These results reveal exogeneous sufficient interfere maturation vessels drive development towards a dysfunctional phenotype. observations deliver further evidence angiopathic factor highlight therapeutic potential blocking diseases characterized pathogenic angiogenesis remodelling.

Язык: Английский

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Promising biomarkers of kawasaki disease: markers that aid in diagnosis

Expert Review of Molecular Diagnostics, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 18, 2024

Introduction Currently the diagnosis of Kawasaki disease is still heavily reliant on clinical criteria which may be subject to interpretation or mimic other common febrile diseases childhood. Biomarkers that can aid in accurate and timely KD are great utility.

Язык: Английский

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