袁俊杰 文献简报21.9.10(2022年-2023年).pdfVIP

袁俊杰 文献简报 2021-09-11 Podocyte-specific KLF4 is required to maintain parietal epithelial cell quiescencein the kidney JesseA.Pace,Robert Bronstein et al. Science DOI:10.1126/sciadv.abg6600 ABSTRACT: Podocyte loss triggering aberrant activation and proliferation of parietal epithelial cells (PECs) is a central pathogenic event in proliferative glomerulopathies. Podocyte-specific Krüppel-like factor 4 (KLF4), a zinc-finger transcription factor, is essential for maintaining podocyte homeostasis and PEC quiescence. Using mice with podocyte-specific knockdown of Klf4, we conducted glomerular RNA-sequencing, tandem mass spectrometry, and single-nucleus RNA-sequencing to identify cell-specific transcriptional changes that trigger PEC activation due to podocyte loss. Integration with in silico chromatin immunoprecipitation identified key ligand-receptor interactions, such as fibronectin 1(FN1)–αVβ6, between podocytes and PECs dependent on KLF4 and downstream signal transducer and activator of transcription 3 (STAT3) signaling. Knockdown of Itgb6 in PECs attenuated PEC activation. Additionally, podocyte-specific induction of human KLF4 or pharmacological inhibition of downstream 袁俊杰 文献简报 2021-09-11 STAT3activation reducedFN1and integrin β 6 (ITGB6) expression and mitigated podocyte loss and PEC activation in mice. Targeting podocyte-PEC crosstalk might be a critical therapeutic strategy in proliferativeglomerulopathies. 足细胞丢失引发壁上皮细胞 (PEC) 的异常激活和增殖，是增殖 性肾小球病的主要致病事件。足细胞特异性 Krüppel 样因子 4 (KLF4) 是一种锌指转录因子，对于维持足细胞稳态和 PEC 静止至 关重要。使用足细胞特异性敲低 Klf4 的小鼠，我们进行了肾小球 RNA 测序、串联质谱法和单核 RNA 测序，以确定由于足细胞丢失 而触发 PEC 激活的细胞特异性转录变化。与计算机染色质免疫沉淀 的整合确定了关键的配体 受体相互作用，例如纤连蛋白- 1(FN1)– αVβ6，在依赖于 KLF4 和下游信号转导器和转录激活因子 3(STA