Transcriptomic profiling of Schlemm’s canal cells reveals a lymphatic-biased identity and three major cell states DOI Creative Commons
Revathi Balasubramanian, Krishnakumar Kizhatil, Taibo Li

и другие.

eLife, Год журнала: 2024, Номер 13

Опубликована: Окт. 16, 2024

Schlemm’s canal (SC) is central in intraocular pressure regulation but requires much characterization. It has distinct inner and outer walls, each composed of endothelial cells (SECs) with different morphologies functions. Recent transcriptomic studies the anterior segment added important knowledge, were limited power by SEC numbers or did not focus on SC. To gain a more comprehensive understanding SC biology, we performed bulk RNA sequencing C57BL/6 J SC, blood vessel, lymphatic from limbal tissue (~4,500 SECs). We also analyzed mouse tissues single-cell single-nucleus (C57BL/6 129/Sj strains), successfully 903 individual SECs. Together, these datasets confirm that molecular characteristics both endothelia phenotype predominating. SECs are enriched pathways regulate cell-cell junction formation pointing to importance junctions determining fluid permeability. Importantly, for first time, our analyses characterize three classes SECs, molecularly distinguishing wall discovering two cell states likely result local environmental differences. Further, based ligand receptor expression patterns, document key interactions between adjacent trabecular meshwork (TM) drainage tissue. Also, present type collection human glaucoma genes. These data provide new foundation will enable functional dissection homeostatic processes mediated as well development therapeutics.

Язык: Английский

Caveolin-1-Mediated LDL Transcytosis across Endothelial Cells in Atherosclerosis DOI Creative Commons
Yifei Zhang, Xiong Jia, Yayu Wang

и другие.

Atherosclerosis, Год журнала: 2025, Номер unknown, С. 119113 - 119113

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

3
Caveolin-1 in endothelial cells: A potential therapeutic target for atherosclerosis DOI Creative Commons
Shu Yan, Si Jin

Heliyon, Год журнала: 2023, Номер 9(8), С. e18653 - e18653

Опубликована: Июль 25, 2023

Atherosclerosis (AS) is a chronic vascular disease characterized by lipid accumulation and the activation of inflammatory response; it remains leading nation-wide cause death. Early in progression AS, stimulation pro-inflammatory agonists (TNF-α, LPS, others), oxidized lipoproteins (ox-LDL), biomechanical stimuli (low shear stress) lead to endothelial cell dysfunction. Consequently, crucial investigate how cells respond different stressors ways alter AS development, as they are earliest respond. Caveolin-1 (Cav1) 21-24-kDa membrane protein located caveolae highly expressed cells, which plays vital role regulating transport, responses, various cellular signaling pathways has atherogenic effects. This review summarizes recent studies on structure physiological functions Cav1 outlines potential mechanisms mediates development. Included roles regulation autophagy, response stress, modulation eNOS/NO axis, transduction pathways. provides rationale for proposing novel target prevention well new ideas therapeutic strategies early AS.

Язык: Английский

Процитировано

19
Signalling pathways and cell death mechanisms in glaucoma: Insights into the molecular pathophysiology DOI Creative Commons
Devaraj Basavarajappa, Caridad Galindo‐Romero, Vivek Gupta

и другие.

Molecular Aspects of Medicine, Год журнала: 2023, Номер 94, С. 101216 - 101216

Опубликована: Окт. 17, 2023

Glaucoma is a complex multifactorial eye disease manifesting in retinal ganglion cell (RGC) death and optic nerve degeneration, ultimately causing irreversible vision loss. Research recent years has significantly enhanced our understanding of RGC degenerative mechanisms glaucoma. It evident that high intraocular pressure (IOP) not the only contributing factor to glaucoma pathogenesis. The equilibrium pro-survival pro-death signalling pathways retina strongly influences function survival RGCs axons Molecular evidence from human tissue analysis range experimental models have contributed unravelling these mechanisms. Accumulating reveals wide molecular can operate -either alone or via intricate networks - induce neurodegeneration. roles several molecules, including neurotrophins, interplay intracellular kinases phosphates, caveolae adapter proteins, serine proteases their inhibitors, nuclear receptors, amyloid beta tau, how dysfunction affects neurons are discussed this review. We further underscore anatomical alterations various animal exhibiting degeneration susceptibility glaucoma-related neuronal damage helped characterise In addition, we also present different regulated play critical role

Язык: Английский

Процитировано

15
The critical roles of caveolin-1 in lung diseases DOI Creative Commons

Jiarun Fan,

Siping Zheng,

M Wang

и другие.

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Сен. 24, 2024

Caveolin-1 (Cav-1), a structural and functional component in the caveolae, plays critical role transcytosis, endocytosis, signal transduction. Cav-1 has been implicated mediation of cellular processes by interacting with variety signaling molecules. is widely expressed endothelial cells, smooth muscle fibroblasts various organs, including lungs. The Cav-1-mediated internalization regulation molecules participate physiological pathological processes. Particularly, MAPK, NF-κB, TGFβ/Smad, eNOS/NO pathways have involved regulatory effects lung diseases. important on lungs indicate that can be potential target for treatment A scaffolding domain peptide CSP7 targeting developed. In this article, we mainly discuss structure its roles diseases, such as pneumonia, acute injury (ALI), asthma, chronic obstructive pulmonary disease (COPD), hypertension, fibrosis, cancer.

Язык: Английский

Процитировано

5
Transcriptomic profiling of Schlemm’s canal cells reveals a lymphatic-biased identity and three major cell states DOI Creative Commons
Revathi Balasubramanian, Krishnakumar Kizhatil, Taibo Li

и другие.

eLife, Год журнала: 2024, Номер 13

Опубликована: Май 9, 2024

Schlemm’s canal (SC) is central in intraocular pressure regulation but requires much characterization. It has distinct inner and outer walls, each composed of endothelial cells (SECs) with different morphologies functions. Recent transcriptomic studies the anterior segment added important knowledge, were limited power by SEC numbers or did not focus on SC. To gain a more comprehensive understanding SC biology, we performed bulk RNA sequencing C57BL/6 J SC, blood vessel, lymphatic from limbal tissue (~4,500 SECs). We also analyzed mouse tissues single-cell single-nucleus (C57BL/6 129/Sj strains), successfully 903 individual SECs. Together, these datasets confirm that molecular characteristics both endothelia phenotype predominating. SECs are enriched pathways regulate cell-cell junction formation pointing to importance junctions determining fluid permeability. Importantly, for first time, our analyses characterize three classes SECs, molecularly distinguishing wall discovering two cell states likely result local environmental differences. Further, based ligand receptor expression patterns, document key interactions between adjacent trabecular meshwork (TM) drainage tissue. Also, present type collection human glaucoma genes. These data provide new foundation will enable functional dissection homeostatic processes mediated as well development therapeutics.

Язык: Английский

Процитировано

4
Identification of Structures Labeled by Indocyanine Green in the Rat Choroid and Retina Can Guide Interpretation of Indocyanine Green Angiography DOI Creative Commons
Dan Mejlachowicz, Patricia Lassiaz, Marta Zola

и другие.

Investigative Ophthalmology & Visual Science, Год журнала: 2024, Номер 65(1), С. 25 - 25

Опубликована: Янв. 9, 2024

Purpose: Indocyanine green (ICG) is an albumin and lipoprotein binding dye absorbing in the far red used angiography to visualize choroidal vessels (ICG [ICGA]). To guide interpretation, ICG transport choroid, RPE, retina of rats was studied. Methods: Two conditions were used: RPE/choroid organoculture, incubated for 45 minutes DMEM medium, 1% fetal bovine serum containing 0.25 mg/mL neural flat-mounts at 1 6 hours after intravenous injection. Early late sequences ICGA recorded until hours. Ultra-deep confocal microscope localize immunohistochemistry performed caveolin-1, tryptase (mast cell marker), tubulin β3 (a nerve marker). Results: In penetrated homogeneously cytoplasm stained membranes RPE. At hour injection, appeared fine granules partly labeled with caveolin-1 decreasing hours, found retinal vessels, faintly inner retina, photoreceptor outer segments colocalized mast cells, immunostained tryptase, accumulated along large β3–labeled bundles. The hypothesis raised on interpretation infrared photography case transthyretin amyloidosis neuropathy. Conclusions: Beside being a vascular dye, transported from RPE toward retina. It stains cells nerves. These observations could help analysis images.

Язык: Английский

Процитировано

3
Targeting Caveolin-1 for enhanced rotator cuff repair: findings from single-cell RNA sequencing DOI Creative Commons

Shanhong Fang,

Songye Wu,

Peng Chen

и другие.

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Март 5, 2025

Abstract Rotator cuff injury (RCI), a prevalent cause of shoulder pain and disability, often leads to significant functional impairments due adipocyte infiltration into the damaged tissue. Caveolin-1 (Cav-1), critical membrane protein, plays role in differentiation lipid metabolism. This study utilized single-cell RNA sequencing (scRNA-seq) investigate heterogeneity cell subpopulations RCI tissues assess regulatory effects Cav-1. The findings revealed that Cav-1 expression negatively correlates with adipogenic activity, its modulation through exercise or targeted therapies can significantly reduce enhance tissue repair. Further, knockout overexpression models demonstrated protein’s impact on key genes involved metabolism, such as Scd1, fatty acid synthase (FASN), peroxisome proliferator-activated receptor gamma (Pparg). Animal studies corroborated these results, showing intervention increased expression, decreased infiltration, promoted structural These insights suggest targeting could offer novel therapeutic strategy for improving outcomes.

Язык: Английский

Процитировано

0
Caveolae: Metabolic Platforms at the Crossroads of Health and Disease DOI Open Access

David Stea,

Alessio D’Alessio

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 2918 - 2918

Опубликована: Март 24, 2025

Caveolae are small flask-shaped invaginations of the plasma membrane enriched in cholesterol and sphingolipids. They play a critical role various cellular processes, including signal transduction, endocytosis, mechanotransduction. Caveolin proteins, specifically Cav-1, Cav-2, Cav-3, addition to their as structural components caveolae, have been found regulate activity signaling molecules. A growing body research has highlighted pivotal caveolae caveolins maintaining metabolic homeostasis. Indeed, studies demonstrated that interact with key insulin signaling, glucose uptake, lipid metabolism, thereby influencing energy production storage. The dysfunction or altered expression associated disorders, obesity, type 2 diabetes, ocular diseases. Remarkably, mutations caveolin genes can disrupt balance, promote oxidative stress, exacerbate dysregulation. This review examines current on molecular mechanisms through which explores involvement pathogenesis discusses potential therapeutic strategies targeting function stabilization restore

Язык: Английский

Процитировано

0
What do You Need to Know after Diabetes and before Diabetic Retinopathy? DOI Creative Commons
Shiyu Zhang, Jia‐Ren Liu, Heng Zhao

и другие.

Aging and Disease, Год журнала: 2025, Номер unknown, С. 0 - 0

Опубликована: Янв. 1, 2025

Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness among individuals with diabetes mellitus. Current clinical diagnostic criteria mainly base on visible vascular structure changes, which are insufficient to identify diabetic patients without DR (NDR) but dysfunctional retinopathy. This review focuses retinal endothelial cells (RECs), the first sense respond elevated blood glucose. As glucose rises, RECs undergo compensatory transitional phases, correspondingly altered molecules likely become biomarkers targets for early prediction treatment NDR article elaborated possible pathophysiological processes focusing summarized recently published reliable screening emerging intervention strategies Additionally, references medication selection lifestyle recommendations this population provided. aims deepen understanding REC biology pathophysiology, emphasizes importance detection intervention, points out future directions improve diagnosis reduce occurrence DR.

Язык: Английский

Процитировано

0
Value and Significance of Hypofluorescent Lesions Seen on Late-Phase Indocyanine Green Angiography DOI Creative Commons
Alain Gaudric

Ophthalmology Science, Год журнала: 2023, Номер 4(2), С. 100406 - 100406

Опубликована: Окт. 3, 2023

Background& Purpose: The hypofluorescence of fundus lesions observed during the late phase indocyanine green angiography (ICGA) in various diseases has often been overlooked or misinterpreted. This article explores significance that are initially isofluorescent early but become hypofluorescent later examination.FindingsPathologies such as multiple evanescent white spot syndrome, acute posterior placoid syphilitic chorioretinitis, chronic central serous chorioretinopathy, choroidal hemangioma, some with drusen, present this phenomenon hypofluorescence.InterpretationThe interpretation ICGA images and role ICG uptake by retinal pigment epithelium (RPE) fluorescence is debated. Experimental evidence suggests accumulates progressively RPE after intravenous injection dye direct contact vitro, making it a potential marker activity. Although exact mechanisms diffusion through choroid its binding to require further investigation, certain provides information on different modalities dysfunction.

Язык: Английский

Процитировано

6