Sepsis-induced inflammatory damage is a crucial cause of acute kidney injury (AKI), and AKI is an ecumenical fearful complication in approximately half of patients with sepsis. CCAAT/enhancer-binding protein β (C/EBPβ) plays roles in regulating acute phase responses and inflammation. However, the role and mechanism of C/EBPβ in AKI are unclear. LPS combined with ATP-treated renal epithelial cells HK2 and cecal ligation-peferation (CLP)-mice were used as models of AKI in vitro and in vivo. Cell damage, the secretion of interleukin-1 beta (IL-1β), IL-18 and cysteinyl aspartate specific proteinase 1 (caspase-1) activity were tested by LDH, ELISA assay and flow cytometry analysis, respectively. The expression levels of TFAM, C/EBPβ, and pyroptosis-related molecules were tested by qRT-PCR and Western blotting. Chromatin immunoprecipitation (ChIP) assessed the interaction between C/EBPβ with TFAM. Hematoxylin-Eosin (H&E) staining detected pathological changes of kidney tissues, and immunohistochemistry measured TFAM and C/EBPβ in mice kidney tissues. C/EBPβ or TFAM were up-regulated in LPS combined with ATP -induced HK2 cells. Knockdown of C/EBPβ could suppress cell injury and the secretion of IL-1β and IL-18 induced by LPS combined with ATP. Furthermore, C/EBPβ up-regulated the expression levels of TFAM via directly binding to TFAM promoter. Overexpression of TFAM reversed the effects of C/EBPβ deficiency on pyroptosis. Knockdown of C/EBPβ could inhibit NLRP3 inflammasome-mediated caspase-1 signaling pathway by inactivating TFAM/RAGE pathway. It was further confirmed in the AKI mice that C/EBPβ and TFAM promoted AKI by activating NLRP3-mediated pyroptosis. The interaction of between C/EBPβ and TFAM facilitated pyroptosis by activating NLRP3/caspase-1 signal axis, thereby promoting the occurrence of AKI.

脓毒症引起的炎性损害是急性肾损伤（AKI）的关键原因，在大约一半的脓毒症患者中，AKI是一种普遍的可怕并发症。CCAAT /增强子结合蛋白β（C /EBPβ）在调节急性期反应和炎症中发挥作用。然而，C /EBPβ在AKI中的作用和机制尚不清楚。LPS结合ATP处理的肾上皮细胞HK2和盲肠结扎-移植（CLP）-小鼠被用作体外和体内AKI模型。通过LDH，ELISA测定和流式细胞术分别检测细胞损伤，白介素-1β（IL-1β），IL-18和半胱氨酸天冬氨酸特异性蛋白酶1（caspase-1）的分泌。用qRT-PCR和Western blotting检测TFAM，C /EBPβ和凋亡相关分子的表达水平。染色质免疫沉淀（ChIP）评估了C /EBPβ与TFAM之间的相互作用。苏木-伊红（H＆E）染色可检测肾组织的病理变化，免疫组织化学检测小鼠肾组织中的TFAM和C /EBPβ。LPS与ATP诱导的HK2细胞结合后，C /EBPβ或TFAM上调。抑制C /EBPβ可以抑制细胞损伤以及LPS结合ATP诱导的IL-1β和IL-18分泌。此外，C /EBPβ通过以下途径上调了TFAM的表达水平：直接与TFAM启动子结合。TFAM的过表达逆转了C /EBPβ缺乏对发烧的影响。抑制C /EBPβ可以通过失活TFAM / RAGE途径抑制NLRP3炎性体介导的caspase-1信号传导途径。在AKI小鼠中进一步证实C /EBPβ和TFAM通过激活NLRP3介导的细胞凋亡来促进AKI。C /EBPβ和TFAM之间的相互作用通过激活NLRP3 / caspase-1信号轴促进了细胞凋亡，从而促进了AKI的发生。