Extracellular status of thrombospondin-2 in type 2 diabetes mellitus and utility as a biomarker in the determination of early diabetic kidney disease

BMC Nephrology

Research

Wenjun Wang¹  Yanxue Bi¹  Didong Zhang¹  Maolan Wu¹  Wanxie Guo¹  Yingchao Zhang¹  Zhen Liu¹  Xinxin Zhang¹  Zhuofeng Lin²  Zhenzhen Lin³  Xuemian Lu³ 

[1] School of Pharmaceutical College, Wenzhou Medical University, Wenzhou, China;School of Pharmaceutical College, Wenzhou Medical University, Wenzhou, China;The 1st Affiliated Hospital of Wenzhou Medical Unversity, South Baixiang Town, 325000, Wenzhou, China;Laboratory Animal Center of Wenzhou Medical University, Wenzhou, China;The 3rd Affiliated Hospital of Wenzhou Medical University (Ruian People’s Hospital), 325200, Wenzhou, China;

关键词: Thrombospondin-2;    Type 2 diabetes;    Early diabetic kidney disease;    Biomarker;    Noninvasive diagnosis;   

DOI  :  10.1186/s12882-023-03216-z

 received in 2023-01-07, accepted in 2023-05-24,  发布年份 2023

来源: Springer

【 摘 要 】

ObjectiveThrombospondin-2 (TSP-2) is a multifunctional matricellular glycoprotein correlated with glucose homeostasis, insulin sensitivity, and estimated glomerular filtration rate. Investigation of the association of TSP-2 with type 2 diabetes mellitus (T2DM) and the potential diagnostic value of serum TSP-2 for detecting early diabetic kidney disease (DKD) is needed.Research design and methodsAn enzyme-linked immunosorbent assay was used for detection serum TSP-2 levels in 494 Chinese T2DM subjects. The protein expression of TSP-2 in the kidney and other tissues were tested by western blotting.ResultsSerum TSP-2 levels in T2DM subjects were significantly higher than in healthy individuals. Serum TSP-2 correlated positively with triglycerides, serum uric acid, creatinine, platelets, and urinary albumin-to-creatinine ratio (UACR), but negatively with estimated glomerular filtration rate, after adjusting for age, sex, and T2DM duration. Logistic regression analysis demonstrated an independent association between serum TSP-2 and early DKD. Furthermore, the high UACR identified at risk of early DKD increased significantly from 0.78 (95%CI 0.73–0.83) to 0.82 (95%CI 0.77–0.86, p < 0.001) when added to a clinical model consisting of TSP-2 and age. In db/db mice, serum TSP-2 levels were elevated. TSP-2 expression was markedly increased in the kidney tissue compared with that in db/m and m/m mice. Furthermore, serum TSP-2 expression correlated well with UACR in mice.ConclusionsTSP-2 is a novel glycoprotein associated with early DKD in patients with T2DM. The paradoxical increase of serum TSP-2 in T2DM individuals may be due to a compensatory response to chronic inflammatory and renal vascular endothelial growth, warranting further investigation.

【 授权许可】

CC BY   
© The Author(s) 2023

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