2型糖尿病肾病患者肾小球与近端小管细胞间的串扰对炎症环境的影响。

IF 6.8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Peong Gang Park, Juhyeon Hwang, Yongjun Kim, Minki Hong, Donghwan Yun, Haein Yoon, Chaelin Kang, Sohyun Bae, Soo Heon Kwak, Yong Chul Kim, Kyung Chul Moon, Dong-Sup Lee, Yon Su Kim, Hee Gyung Kang, Hyun Je Kim, Seung Seok Han
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引用次数: 0

摘要

背景:由于2型糖尿病肾病(T2DKD)治疗药物的可用性有限,需要从实验模型和创新技术中获得进一步的知识。为了解决这一问题,单细胞RNA测序(scRNA-seq)已经专门应用于转基因糖尿病肾病模型,但未应用于代表T2DKD的诱导模型。在此,我们分析了诱导T2DKD模型的scRNA-seq和其他实验,并在人类来源的生物标本中验证了结果。方法:采用高脂饮食联合链脲佐菌素模拟T2DKD模型。进行scRNA-seq、组织学和流式细胞术分析,并将结果与对照小鼠进行比较。这些发现随后被应用于人类T2DKD肾脏。结果:生化和组织学分析揭示了T2DKD的早期特征,如高滤过、蛋白尿增加、肾小球肿大和间质纤维化。scRNA-seq发现近端小管分泌多种趋化因子,可能与肾小球的串扰有关。值得注意的是,C-X-C基序趋化因子12 (CXCL12)在潜在促进t细胞募集中发挥了关键作用。流式细胞术证实T2DKD模型肾内有t细胞浸润。这一发现在人体肾组织活检中得到进一步证实,显示CXCL12水平升高与T2DKD进展之间存在相关性。结论:诱导的T2DKD模型强调了cxcl12介导的t细胞浸润的关键作用,这种浸润源于近端小管和肾小球之间的串扰。这些数据为未来的研究奠定了基础,为T2DKD的治疗靶点提供了希望。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Inflammatory Milieu by Crosstalk between Glomerulus and Proximal Tubular Cells in Type 2 Diabetes Mellitus Kidney Disease.

Background: Due to the limited availability of therapeutic agents for type 2 diabetic kidney disease (T2DKD), there is a need for further knowledge derived from experimental models and innovative techniques. In addressing this issue, single-cell RNA sequencing (scRNA-seq) has been exclusively applied to a genetically modified diabetic kidney disease model, but not to an induced model representing T2DKD. Herein, we analyzed scRNA-seq and other experiments from an induced T2DKD model and validated the results in human-derived biospecimens.

Methods: The model was induced by combining a high-fat diet with streptozotocin to simulate induced T2DKD. scRNA-seq, histological, and flow cytometric analyses were conducted, and the results were compared with control mice. The findings were then applied to human T2DKD kidneys.

Results: Biochemical and histological analyses unveiled early-stage T2DKD features, such as hyperfiltration, increased proteinuria, glomerulomegaly, and interstitial fibrosis. scRNA-seq identified that proximal tubules secreted a variety of chemokines, potentially in response to crosstalk with glomeruli. Notably, C-X-C motif chemokine 12 (CXCL12) emerged as a key player in potentially promoting T-cell recruitment. Flow cytometry substantiated T-cell infiltration into the kidney of the T2DKD model. This finding was further corroborated in human biopsied kidney tissues, showing a correlation between elevated CXCL12 levels and T2DKD progression.

Conclusion: The induced T2DKD model highlights the pivotal role of CXCL12-mediated T-cell infiltration, stemming from the crosstalk between proximal tubules and glomeruli. This data serves as a foundation for future studies, promising a therapeutic target for T2DKD.

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来源期刊
Diabetes & Metabolism Journal
Diabetes & Metabolism Journal Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
10.40
自引率
6.80%
发文量
92
审稿时长
52 weeks
期刊介绍: The aims of the Diabetes & Metabolism Journal are to contribute to the cure of and education about diabetes mellitus, and the advancement of diabetology through the sharing of scientific information on the latest developments in diabetology among members of the Korean Diabetes Association and other international societies. The Journal publishes articles on basic and clinical studies, focusing on areas such as metabolism, epidemiology, pathogenesis, complications, and treatments relevant to diabetes mellitus. It also publishes articles covering obesity and cardiovascular disease. Articles on translational research and timely issues including ubiquitous care or new technology in the management of diabetes and metabolic disorders are welcome. In addition, genome research, meta-analysis, and randomized controlled studies are welcome for publication. The editorial board invites articles from international research or clinical study groups. Publication is determined by the editors and peer reviewers, who are experts in their specific fields of diabetology.
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