Renal tubular epithelial cell quality control mechanisms as therapeutic targets in renal fibrosis

作者：Yini Bao, Qiyuan Shan, Keda Lu, Qiao Yang, Ying Liang, Haodan Kuang, Lu Wang, Min Hao, Mengyun Peng, Shuosheng Zhang, Gang Cao · 发表于：Journal of Pharmaceutical Analysis · 年份：2024 · DOI：10.1016/j.jpha.2024.01.001 · 被引用次数：34 · 研究领域：Phagocytosis and Immune Regulation、Endoplasmic Reticulum Stress and Disease、Renal Diseases and Glomerulopathies

Renal fibrosis is a devastating consequence of progressive chronic kidney disease, representing a major public health challenge worldwide. The underlying mechanisms in the pathogenesis of renal fibrosis remain unclear, and effective treatments are still lacking. Renal tubular epithelial cells (RTECs) maintain kidney function, and their dysfunction has emerged as a critical contributor to renal fibrosis. Cellular quality control comprises several components, including telomere homeostasis, ubiquitin-proteasome system (UPS), autophagy, mitochondrial homeostasis (mitophagy and mitochondrial metabolism), endoplasmic reticulum (ER, unfolded protein response), and lysosomes. Failures in the cellular quality control of RTECs, including DNA, protein, and organelle damage, exert profibrotic functions by leading to senescence, defective autophagy, ER stress, mitochondrial and lysosomal dysfunction, apoptosis, fibroblast activation, and immune cell recruitment. In this review, we summarize recent advances in understanding the role of quality control components and intercellular crosstalk networks in RTECs, within the context of renal fibrosis.