Mitochondrial homeostasis dysfunctions during the epithelial-mesenchymal transition process in lens epithelial cells

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research Pub Date : 2025-08-19 DOI:10.1016/j.exer.2025.110583

Hang Xie , Rong Huang , Ke Xu , Lei Du , Xingyu Yang , Weichen Xu , Xiaoyu Guo , Guojing Lu , Tingting Fan , Changzheng Chen

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Abstract

Lens epithelial cells (LECs), the main mitochondria-containing cells in the lens, play a vital role in maintaining lens transparency. Mitochondrial homeostasis is essential for cellular function, yet its changes during epithelial-mesenchymal transition (EMT) in LECs remain unclear. In this study, EMT was induced in LECs using transforming growth factor-β2 (TGF-β2), and mitochondrial function was evaluated through ROS, ATP levels, membrane potential, Mitotracker staining, and electron microscopy. TGF-β2 treatment resulted in mitochondrial dysfunction, evidenced by increased ROS, decreased ATP production, and reduced membrane potential. Mitochondria changed from elongated tubular shapes to fragmented spherical forms. Mitochondrial dynamics were disrupted, with downregulation of fusion proteins (Mfn1, Mfn2, Opa1) and upregulation of fission protein Drp1. Mitophagy was impaired despite activation of the PINK1/Parkin pathway, and mitochondrial biogenesis was suppressed, as shown by decreased expression of PGC-1α and TFAM and reduced mtDNA copy number. These findings highlight a significant imbalance in mitochondrial homeostasis during TGF-β2-induced EMT in LECs, which may contribute to lens opacity and fibrotic cataract formation, offering potential targets for therapeutic intervention.

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晶状体上皮细胞上皮-间质转化过程中线粒体稳态失调

晶状体上皮细胞（LECs）是晶状体中主要的含线粒体细胞，在维持晶状体透明度中起着至关重要的作用。线粒体稳态对细胞功能至关重要，但其在上皮-间质转化（EMT）过程中的变化尚不清楚。本研究采用转化生长因子-β2 （TGF-β2）诱导lec细胞发生EMT，并通过ROS、ATP水平、膜电位、Mitotracker染色、电镜等方法评价线粒体功能。TGF-β2处理导致线粒体功能障碍，表现为ROS增加，ATP生成减少，膜电位降低。线粒体由细长的管状变为破碎的球形。线粒体动力学被破坏，融合蛋白（Mfn1, Mfn2, Opa1）下调，裂变蛋白Drp1上调。尽管激活了PINK1/Parkin通路，但线粒体自噬受损，线粒体生物发生受到抑制，表现为PGC-1α和TFAM的表达降低，mtDNA拷贝数减少。这些发现强调了TGF-β2诱导的lec EMT过程中线粒体稳态的显著失衡，这可能导致晶状体混浊和纤维化性白内障的形成，为治疗干预提供了潜在的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental eye research 医学-眼科学

CiteScore

6.80

自引率

5.90%

发文量

323

审稿时长

66 days

期刊介绍： The primary goal of Experimental Eye Research is to publish original research papers on all aspects of experimental biology of the eye and ocular tissues that seek to define the mechanisms of normal function and/or disease. Studies of ocular tissues that encompass the disciplines of cell biology, developmental biology, genetics, molecular biology, physiology, biochemistry, biophysics, immunology or microbiology are most welcomed. Manuscripts that are purely clinical or in a surgical area of ophthalmology are not appropriate for submission to Experimental Eye Research and if received will be returned without review.