Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116011, PR China.
Mol Med. 2024 Nov 20;30(1):222. doi: 10.1186/s10020-024-00994-6.
Activation of pericytes leads to renal interstitial fibrosis, but the regulatory mechanism of pericytes in the progression from AKI to CKD remains poorly understood. CD36 activation plays a role in the progression of CKD. However, the significance of CD36 during AKI-CKD, especially in pericyte, remains to be fully defined.
GEO and DISCO database were used to analyze the expression of CD36 in pericyte during AKI-CKD; IRI to conduct AKI-CKD mouse model; Hypoxia/Reoxygenation (H/R) to induce the cell model; RT-qPCR and Western blotting to detect gene expression; IP and confocal-IF to determine the core fucosylation (CF) level of CD36. Flow cytometry (AV/PI staining) to detect the cell apoptosis and JC-1 staining to react to the change of mitochondrial membrane potential.
During AKI to CKD progression, CD36 expression in pericytes is higher and may be influenced by CF. Moreover, we confirmed the positive association of CD36 expression with pericyte-myofibroblast transition and the progression of AKI-CKD in an IRI mouse model and hypoxia/reoxygenation (H/R) pericytes. Notably, we discovered that FUT8 upregulates both CD36 expression and its CF level, contributing to the activation of the mitochondrial-dependent apoptosis signaling pathway in pericytes, ultimately leading to the progression of AKI-CKD.
These results further identify FUT8 and CD36 as potential targets for the treatment in the progression of AKI-CKD.
周细胞的激活会导致肾间质纤维化，但周细胞在急性肾损伤（AKI）向慢性肾脏病（CKD）进展中的调控机制仍知之甚少。CD36 的激活在 CKD 的进展中起作用。然而，CD36 在 AKI-CKD 中的意义，特别是在周细胞中的意义，仍有待充分定义。
使用 GEO 和 DISCO 数据库分析 AKI-CKD 期间周细胞中 CD36 的表达；使用 IRI 构建 AKI-CKD 小鼠模型；使用低氧/复氧（H/R）诱导细胞模型；RT-qPCR 和 Western blot 检测基因表达；免疫沉淀（IP）和共聚焦免疫荧光（IF）检测 CD36 的核心岩藻糖基化（CF）水平。流式细胞术（AV/PI 染色）检测细胞凋亡，JC-1 染色反应线粒体膜电位变化。
在 AKI 向 CKD 进展过程中，周细胞中 CD36 的表达增加，可能受到 CF 的影响。此外，我们在 IRI 小鼠模型和低氧/复氧（H/R）周细胞中证实了 CD36 表达与周细胞-肌成纤维细胞转化和 AKI-CKD 进展的正相关。值得注意的是，我们发现 FUT8 上调了 CD36 的表达及其 CF 水平，促进了周细胞中线粒体依赖性凋亡信号通路的激活，最终导致 AKI-CKD 的进展。
这些结果进一步将 FUT8 和 CD36 确定为 AKI-CKD 进展治疗的潜在靶点。
