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Desmosterol-driven atypical macrophage polarization regulates podocyte dynamics in diabetic nephropathy
Molecular Biology Reports ( IF 2.6 ) Pub Date : 2024-01-27 , DOI: 10.1007/s11033-023-09198-3
Huiying Qi 1
Affiliation  

Background

Diabetic nephropathy (DN) stands as a leading diabetes complication, with macrophages intricately involved in its evolution. While glucose metabolism’s impact on macrophage activity is well-established, cholesterol metabolism’s contributions remain less explored. Our study seeks to elucidate this association.

Methods and results

Methods and Results: Gene expression analysis of monocytes from the blood of both normal and diabetic patients was conducted using public databases, showing that cholesterol metabolism pathways, especially Bloch and Kandutsch-Russell, were more altered in diabetic monocytes/macrophages than glucose-responsive pathways. When bone marrow-derived macrophages (BMDMs) were subjected to desmosterol, they exhibited an unconventional polarization. These BMDMs displayed heightened levels of both M1-related pro-inflammatory cytokines and M2-linked anti-inflammatory factors. Further, in co-culture, desmosterol-conditioned BMDMs paralleled M2 macrophages in augmenting Ki-67 + podocyte populations while mimicking M1 macrophages in elevating TUNEL + apoptotic podocytes. Comparable outcomes on podocytes were obtained using conditioned media from the respective BMDMs.

Conclusions

Our data underscores the pivotal role of cholesterol metabolism, particularly via desmosterol, in steering macrophages toward an unconventional polarization marked by both inflammatory and regulatory traits. Such unique macrophage behavior concurrently impacts podocyte proliferation and apoptosis, shedding fresh light on DN pathogenesis and hinting at potential therapeutic interventions.



中文翻译:


去莫斯特罗驱动的非典型巨噬细胞极化调节糖尿病肾病中的足细胞动力学


 背景


糖尿病肾病 (DN) 是一种主要的糖尿病并发症,巨噬细胞与其演变有着错综复杂的关系。虽然葡萄糖代谢对巨噬细胞活性的影响已得到充分证实,但胆固醇代谢的贡献仍然较少被探索。我们的研究试图阐明这种关联。

 方法和结果


方法和结果: 使用公共数据库对正常和糖尿病患者血液中单核细胞的基因表达分析,显示胆固醇代谢途径,尤其是 Bloch 和 Kandutsch-Russell,在糖尿病单核细胞/巨噬细胞中比葡萄糖反应途径改变更大。当骨髓来源的巨噬细胞 (BMDM) 接受 desmosterol 时,它们表现出非常规的极化。这些 BMDM 显示 M1 相关促炎细胞因子和 M2 相关抗炎因子的水平升高。此外,在共培养中,桥甾醇条件的 BMDM 在增加 Ki-67 + 足细胞群方面与 M2 巨噬细胞平行,同时在提高 TUNEL + 凋亡足细胞方面模拟 M1 巨噬细胞。使用来自相应 BMDM 的条件培养基获得足细胞的可比结果。

 结论


我们的数据强调了胆固醇代谢的关键作用,特别是通过桥甾醇,在引导巨噬细胞走向以炎症和调节特征为标志的非常规极化方面。这种独特的巨噬细胞行为同时影响足细胞增殖和凋亡,为 DN 的发病机制提供了新的思路,并暗示了潜在的治疗干预。

更新日期:2024-01-27
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