LPS-induced senescence of macrophages aggravates calcification and senescence of vascular smooth muscle cells via IFITM3.

IF 3 3区 医学 Q1 UROLOGY & NEPHROLOGY
Renal Failure Pub Date : 2024-12-01 Epub Date: 2024-07-08 DOI:10.1080/0886022X.2024.2367708
Ya-Ping Fang, Xin Yang, Ying Zhang, Xiao-Dong Zhu, Xiao-Xu Wang, Yan Liu, Wen Shi, Jia-Yi Huang, Yu Zhao, Xiao-Liang Zhang
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引用次数: 0

Abstract

Background: Cellular senescence, macrophages infiltration, and vascular smooth muscle cells (VSMCs) osteogenic transdifferentiation participate in the pathophysiology of vascular calcification in chronic kidney disease (CKD). Senescent macrophages are involved in the regulation of inflammation in pathological diseases. In addition, senescent cells spread senescence to neighboring cells via Interferon-induced transmembrane protein3 (IFITM3). However, the role of senescent macrophages and IFITM3 in VSMCs calcification remains unexplored.

Aims: To explore the hypothesis that senescent macrophages contribute to the calcification and senescence of VSMCs via IFITM3.

Methods: Here, the macrophage senescence model was established using Lipopolysaccharides (LPS). The VSMCs were subjected to supernatants from macrophages (MCFS) or LPS-induced macrophages (LPS-MCFS) in the presence or absence of calcifying media (CM). Senescence-associated β-galactosidase (SA-β-gal), Alizarin red (AR), immunofluorescent staining, and western blot were used to identify cell senescence and calcification.

Results: The expression of IFITM3 was significantly increased in LPS-induced macrophages and the supernatants. The VSMCs transdifferentiated into osteogenic phenotype, expressing higher osteogenic differentiation markers (RUNX2) and lower VSMCs constructive makers (SM22α) when cultured with senescent macrophages supernatants. Also, senescence markers (p16 and p21) in VSMCs were significantly increased by senescent macrophages supernatants treated. However, IFITM3 knockdown inhibited this process.

Conclusions: Our study showed that LPS-induced senescence of macrophages accelerated the calcification of VSMCs via IFITM3. These data provide a new perspective linking VC and aging, which may provide clues for diagnosing and treating accelerated vascular aging in patients with CKD.

LPS 诱导的巨噬细胞衰老会通过 IFITM3 加剧血管平滑肌细胞的钙化和衰老。
背景:细胞衰老、巨噬细胞浸润和血管平滑肌细胞(VSMCs)成骨转分化参与了慢性肾脏病(CKD)血管钙化的病理生理学过程。衰老的巨噬细胞参与病理疾病中炎症的调节。此外,衰老细胞通过干扰素诱导跨膜蛋白3(IFITM3)将衰老扩散到邻近细胞。目的:探讨衰老巨噬细胞通过 IFITM3 促进 VSMCs 钙化和衰老的假说。在有或没有钙化培养基(CM)的情况下,将 VSMCs 放入巨噬细胞(MCFS)或 LPS 诱导的巨噬细胞(LPS-MCFS)的上清液中。衰老相关的β-半乳糖苷酶(SA-β-gal)、茜素红(AR)、免疫荧光染色和免疫印迹用于鉴定细胞衰老和钙化:结果:在 LPS 诱导的巨噬细胞和上清液中,IFITM3 的表达明显增加。用衰老巨噬细胞上清培养的 VSMCs 转分化为成骨表型,表达较高的成骨分化标志物(RUNX2)和较低的 VSMCs 构建者(SM22α)。此外,衰老巨噬细胞上清液处理后,VSMCs 中的衰老标记物(p16 和 p21)明显增加。结论:我们的研究表明,LPS 诱导的巨噬细胞衰老通过 IFITM3 加速了 VSMCs 的钙化。这些数据提供了一个将血管钙化和衰老联系起来的新视角,可能为诊断和治疗慢性肾脏病患者血管加速衰老提供线索。
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来源期刊
Renal Failure
Renal Failure 医学-泌尿学与肾脏学
CiteScore
3.90
自引率
13.30%
发文量
374
审稿时长
1 months
期刊介绍: Renal Failure primarily concentrates on acute renal injury and its consequence, but also addresses advances in the fields of chronic renal failure, hypertension, and renal transplantation. Bringing together both clinical and experimental aspects of renal failure, this publication presents timely, practical information on pathology and pathophysiology of acute renal failure; nephrotoxicity of drugs and other substances; prevention, treatment, and therapy of renal failure; renal failure in association with transplantation, hypertension, and diabetes mellitus.
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