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

• Published in: BMC nephrology Vol. 24; no. 1; p. 154
• Main Authors: Lin, Zhenzhen, Zhang, Didong, Zhang, Xinxin, Guo, Wanxie, Wang, Wenjun, Zhang, Yingchao, Liu, Zhen, Bi, Yanxue, Wu, Maolan, Lin, Zhuofeng, Lu, Xuemian
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 31.05.2023; BioMed Central; BMC
• Subjects: Analysis; Angiogenesis; Animals; Biochemistry; Biological markers; Biomarker; Biomarkers; Blood & organ donations; Blood pressure; Body mass index; Care and treatment; Cell growth; Cholesterol; Creatinine; Creatinine - blood; Creatinine - urine; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - diagnosis; Diabetic nephropathies; Diabetic Nephropathies - diagnosis; Diabetic Nephropathies - etiology; Diabetic nephropathy; Diagnosis; Early diabetic kidney disease; Enzyme-linked immunosorbent assay; Extracellular matrix; Glomerular filtration rate; Glucose; Glycoproteins; Growth factors; Health aspects; Health care; High density lipoprotein; Homeostasis; Humans; Inflammation; Kidney diseases; Laboratory animals; Measurement; Mice; Nephrology; Noninvasive diagnosis; Proteins; Regression analysis; Software; Thrombosis; Thrombospondin; Thrombospondin-2; Thrombospondins - blood; Triglycerides; Type 2 diabetes; Uric acid; Uric Acid - blood; Western blotting; China; Type 2 diabetes; Early diabetic kidney disease; Noninvasive diagnosis; Thrombospondin-2; Biomarker
• ISSN: 1471-2369; 1471-2369
• DOI: 10.1186/s12882-023-03216-z

Thrombospondin-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. An 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. Serum 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. TSP-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.