Finerenone Regulates Macrophage-Tubular Crosstalk in Diabetic Nephropathy via the AMPK/PKM2 Pathway.

IF 0.9 4区医学 Q4 MEDICAL LABORATORY TECHNOLOGY

Annals of clinical and laboratory science Pub Date : 2026-07-01

Jimei Tang, Lifei Zhu

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引用次数: 0

Abstract

Objective: To clarify how finerenone (FIN) regulates macrophage-renal tubular crosstalk in diabetic nephropathy (DN) via the AMPK/PKM2 pathway.

Methods: Diabetes was experimentally induced in C57BL/6J mice via intraperitoneal injection of streptozotocin after high-fat diet feeding for eight weeks. FIN treatment was initiated five days after diabetes induction and continued for 12 weeks. DN in mice was evaluated by measuring blood glucose, urea nitrogen, creatinine, and urinary microalbumin, together with histopathological evaluation. Mouse BMDMs were exposed to high glucose (HG) and treated with FIN and the AMPK inhibitor compound C (CC). Polarization of BMDMs was assessed by immunofluorescence and western blot. A co-culture system was established by treating mouse renal tubular epithelial cells (RTECs) with conditioned medium (CM) from BMDMs. The viability of mouse RTECs, the expression levels of NGAL and KIM-1, and apoptosis-related proteins in mouse RTECs were measured.

Results: FIN alleviated renal injury in mice with DN. Experimental evidence indicated that FIN inhibited macrophage M1 polarization and promoted AMPK/PKM2 pathway activation. In HG-stimulated FIN-treated BMDMs, CC significantly suppressed the activity of the AMPK/PKM2 pathway and promoted M1 polarization of BMDMs. In the co-culture system, the CM from HG-treated BMDMs inhibited mouse RTECs viability, increased the expression of KIM-1 and NGAL proteins, and induced apoptosis. In contrast, the CM from HG- and FIN-treated BMDMs enhanced mouse RTECs viability, reduced the expression of KIM-1 and NGAL proteins, and suppressed apoptosis.

Conclusion: FIN ameliorates DN by regulating the AMPK/PKM2 pathway to influence macrophage polarization and attenuate RTEC injury.

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芬烯酮通过AMPK/PKM2通路调节糖尿病肾病中的巨噬细胞-小管串扰。

目的：阐明芬烯酮（FIN）如何通过AMPK/PKM2通路调节糖尿病肾病（DN）中巨噬细胞-肾小管串扰。方法：采用高脂饲料喂养8周后，腹腔注射链脲佐菌素诱导C57BL/6J小鼠发生糖尿病。FIN治疗在糖尿病诱导后5天开始，持续12周。通过测定血糖、尿素氮、肌酐、尿微量白蛋白及组织病理学评价小鼠DN。小鼠bmdm暴露于高糖（HG），并用FIN和AMPK抑制剂化合物C （CC）处理。免疫荧光和western blot检测BMDMs的极化情况。用bmdm的条件培养基（CM）处理小鼠肾小管上皮细胞（RTECs），建立共培养体系。测定小鼠RTECs的活力、NGAL、KIM-1表达水平和凋亡相关蛋白水平。结果：FIN可减轻DN小鼠肾损伤。实验证据表明，FIN抑制巨噬细胞M1极化，促进AMPK/PKM2通路激活。在hg刺激的fin处理BMDMs中，CC显著抑制AMPK/PKM2通路的活性，促进BMDMs的M1极化。在共培养体系中，hg处理bmdm的CM抑制小鼠RTECs活力，增加KIM-1和NGAL蛋白的表达，诱导细胞凋亡。相比之下，HG和fin处理的bmdm的CM增强了小鼠RTECs的活力，降低了KIM-1和NGAL蛋白的表达，并抑制了细胞凋亡。结论：FIN通过调节AMPK/PKM2通路影响巨噬细胞极化，减轻RTEC损伤，改善DN。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of clinical and laboratory science 医学-医学实验技术

CiteScore

1.60

自引率

0.00%

发文量

112

审稿时长

6-12 weeks

期刊介绍： The Annals of Clinical & Laboratory Science welcomes manuscripts that report research in clinical science, including pathology, clinical chemistry, biotechnology, molecular biology, cytogenetics, microbiology, immunology, hematology, transfusion medicine, organ and tissue transplantation, therapeutics, toxicology, and clinical informatics.