医学
纤维化
癌症研究
移植
下调和上调
化学
细胞生物学
内分泌学
内科学
生物
生物化学
基因
作者
Yang-He Zhang,Bin Liu,Qingfei Meng,Dan Zhang,Hongxia Yang,Guangtao Li,Yuxiong Wang,Mingdi Liu,Nian Liu,Jinyu Yu,Si Liu,Honglan Zhou,Zhi‐Xiang Xu,Yishu Wang
标识
DOI:10.1016/j.phrs.2024.107105
摘要
Chronic interstitial fibrosis presents a significant challenge to the long-term survival of transplanted kidneys. Our research has shown that reduced expression of acyl-coenzyme A oxidase 1 (ACOX1), which is the rate-limiting enzyme in the peroxisomal fatty acid β-oxidation pathway, contributes to the development of fibrosis in renal allografts. ACOX1 deficiency leads to lipid accumulation and excessive oxidation of polyunsaturated fatty acids (PUFAs), which mediate epithelial–mesenchymal transition (EMT) and extracellular matrix (ECM) reorganization respectively, thus causing fibrosis in renal allografts. Furthermore, activation of Toll-like receptor 4 (TLR4)-nuclear factor kappa-B (NF-κB) signaling induced ACOX1 downregulation in a DNA methyltransferase 1 (DNMT1)-dependent manner. Overconsumption of PUFA resulted in endoplasmic reticulum (ER) stress, which played a vital role in facilitating ECM reorganization. Supplementation with PUFAs contributed to delayed fibrosis in a rat model of renal transplantation. The study provides a novel therapeutic approach that can delay chronic interstitial fibrosis in renal allografts by targeting the disorder of lipid metabolism.
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