A Multifaceted Giant Protein Microtubule-Actin Cross-Linking Factor 1

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3204 - 3204

Опубликована: Март 30, 2025

Microtubule-actin cross-linking factor 1 (MACF1), also known as actin family protein 7 (ACF7), is a giant cytolinker with multiple conserved domains that can orchestrate cytoskeletal networks of and microtubules. MACF1 involved in various biological processes, including cell polarity, cell–cell connection, proliferation, migration, vesicle transport, signal transduction, neuronal development. In this review, we updated the physiological pathological roles MACF1, highlighting components signaling pathways involved. Novel evidence showed diverse human diseases, congenital myasthenic syndrome, premature ovarian insufficiency, spectraplakinopathy, osteoporosis, proliferative diabetic retinopathy, types cancer. We reviewed its involvement adhesome formation, bone aging, tooth addition, plays other roles, functioning biomarker for prediction infections patients burns marker genome selection breeding. These studies reinforce idea bona fide versatile, multifaceted protein. Identifying additional functions would finally help treatment diseases caused by defects.

Язык: Английский

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m6A demethylase ALKBH5 reduces ferroptosis in diabetic retinopathy through the m6A‐YTHDF1‐ACSL4 axis

Diabetic Medicine, Год журнала: 2025, Номер unknown

Опубликована: Апрель 10, 2025

Abstract Aim Diabetic retinopathy (DR) represents the main ocular complication of diabetes. Targeting ferroptosis is a promising treatment choice for various diabetic complications. N6‐methyladenosine (m6A) demethylase alkylation repair homolog protein 5 (ALKBH5) functions as pivotal regulator ferroptosis, and we investigated its role molecular mechanisms in DR. Methods A DR mouse model was developed by streptozotocin (STZ) intraperitoneal injection. High glucose (HG)‐induced human retinal pigment epithelial cells (ARPE‐19) were used vitro . ALKBH5, YTH RNA binding 1 (YTHDF1) acyl‐CoA synthetase long‐chain family member 4 (ACSL4) expression levels examined RT‐qPCR Western blot. The biological ALKBH5 vivo gain‐of‐function loss‐of‐function analyses. ALKBH5's downstream regulatory detected bioinformatics analysis, pull‐down, MeRIP‐qPCR actinomycin D assay. Results under‐expressed while YTHDF1 ACSL4 up‐regulated tissues STZ‐induced mice HG‐stimulated ARPE‐19 cells. Ectopically expressed or knockdown partially reversed increased , evidenced decreased Fe 2+ malondialdehyde reactive oxygen species yet glutathione level. mediated m6A modification mRNA disrupted stability YTHDF1‐dependent manner. Importantly, data demonstrated that overexpression repressed alleviated down‐regulating ACSL4. Conclusion These findings suggest may delay progression reducing through m6A‐YTHDF1‐ACSL4 axis, offering therapeutic paradigms

Язык: Английский

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Genetic Evidence Supporting a Causal Association Between mTORC1-Dependent Circulating Protein Levels and Diabetic Retinopathy

Translational Vision Science & Technology, Год журнала: 2025, Номер 14(5), С. 4 - 4

Опубликована: Май 2, 2025

The mechanistic target of rapamycin (mTOR) signaling pathway is essential for the onset and progression diabetic retinopathy (DR). Nevertheless, impact mTORC1 downstream proteins in DR remains uncertain. Therefore, we performed a Mendelian randomization (MR) research to assess causal effect on risk. Summary statistics were obtained from INTERVAL FinnGen studies (14,584 patients 176,010 controls), respectively. We used various MR techniques, including inverse-variance-weighted, weighted median, MR-Egger. Possible pleiotropy heterogeneity identified through sensitivity analysis. Genetically predicted eIF4E was positively correlated risk (odds ratio = 1.057; 95% confidence interval, 1.008-1.109; P 0.022]. No relationship has been shown circulating RP-S6K, eIF4G, eIF4A, eIF4E-BP eIF4B levels with formation. There no or unbalanced level identified. Higher serum promote DR, proposing that pharmacological inhibition activity may be prospective therapeutic strategy. present study highlighted role development establishing foundation basic into targets.

Язык: Английский

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Correlation between macular perfusion status and visual acuity in retinal vein occlusion.

PubMed, Год журнала: 2024, Номер 49(6), С. 943 - 950

Опубликована: Июнь 28, 2024

Retinal vein occlusion (RVO) is the second most common retinal vascular disease worldwide, and perfusion status closely related to prognosis of disease. Macular particularly correlated with visual acuity. This study aims investigate changes in macular indicators RVO using optical coherence tomography angiography (OCTA) analyze correlation between

Язык: Английский

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