Increased urinary excretion of hedgehog interacting protein (uHhip) in early diabetic kidney disease
| Autor: | Isabelle Chenier, Shao-Ling Zhang, Jean Ethier, Stéphan Troyanov, Min-Chun Liao, Xin-Ping Zhao, Shiao-Ying Chang, Jean-François Cailhier, Kana N. Miyata, Jean-Baptiste Lattouf, John S.D. Chan, Jean-Louis Chiasson, Julie R. Ingelfinger, Chao-Sheng Lo |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Urinary system Kidney Glomerulus Urine Kidney Transforming Growth Factor beta1 Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Physiology (medical) Diabetes mellitus Internal medicine Albuminuria Animals Humans Medicine Diabetic Nephropathies Prospective Studies Aged Creatinine Membrane Glycoproteins business.industry Biochemistry (medical) Public Health Environmental and Occupational Health Albumin Endothelial Cells General Medicine Middle Aged medicine.disease Mice Inbred C57BL 030104 developmental biology Endocrinology chemistry 030220 oncology & carcinogenesis Female Microalbuminuria medicine.symptom Carrier Proteins business Hedgehog interacting protein |
| Zdroj: | Translational Research. 217:1-10 |
| ISSN: | 1931-5244 |
| DOI: | 10.1016/j.trsl.2019.11.001 |
| Popis: | Glomerular endothelial cell (GEC) dysfunction occurs in diabetic kidney disease (DKD) and generally precedes albuminuria. We recently reported that hedgehog interacting protein (Hhip), highly expressed in GECs, contributes to DKD development in diabetic mice. Here, we hypothesized that urinary Hhip (uHhip) could identify early DKD; we tested uHhip in mice and humans with diabetes (DM). In both type 1 (Akita) and type 2 (db/db) DM mice, uHhip is elevated prior to the development of albuminuria, while non-DM controls excrete minimal amount of uHhip. In 87 type 2 DM patients and 39 healthy controls, the uHhip/creatinine (Cr) ratio provides a significant discrimination between non-DM and DM groups; 0 [0-69.5] in non-DM, 9.9 [1.7-39.5] in normoalbuminuric DM, 167.7 [95.7-558.7] in microalbuminuric DM, and 207.9 [0-957.2] in macroalbuminuric DM (median [IQR] ng/mmol, P < 0.0001). The log-uHhip/Cr is positively correlated with urine albumin/Cr ratio (UACR) (spearman correlation coefficient 0.47, P < 0.0001). The log-uHhip/Cr is also associated with eGFR, pulse pressure, and urinary cytokines (IL-1β, IL-6, IL-8, and TGFβ1) independent of UACR. By immunostaining, Hhip is localized in glomeruli and tubules, and is increased in human DM kidneys compared with non-DM kidneys. TGFβ1 shares the similar staining pattern as Hhip in human DM kidneys. Thus, uHhip appears to be a novel indicator of diabetic GEC injury and is elevated in early DKD before the development of microalbuminuria in mice and humans. Clinical value for detecting early DKD warrants further investigation. |
| Databáze: | OpenAIRE |
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