Deletion of Smad3 prevents renal fibrosis and inflammation in type 2 diabetic nephropathy
| Autor: | Hui-Yao Lan, Bi-Hua Xu, Yong-Ke You, Xiao-Ru Huang, Ronald C.W. Ma, Jingyi Sheng, Qingwen Wang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Endocrinology Diabetes and Metabolism Renal function 030209 endocrinology & metabolism Kidney Diabetes Mellitus Experimental Pathogenesis Diabetic nephropathy 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Endocrinology Fibrosis Internal medicine medicine Renal fibrosis Albuminuria Animals Diabetic Nephropathies Smad3 Protein Mice Knockout Creatinine integumentary system business.industry medicine.disease Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure chemistry Diabetes Mellitus Type 2 Microalbuminuria Female business Gene Deletion |
| Zdroj: | Metabolism: clinical and experimental. 103 |
| ISSN: | 1532-8600 |
| Popis: | Background Transforming growth factor (TGF)-β/Smad3 signaling is highly activated in kidneys of patients with type 2 diabetic nephropathy (T2DN), however, the precise role of Smad3 in the pathogenesis of diabetic nephropathy remains unclear. Methods Smad3 knockout (KO)-db/db mice were generated by intercrossing of male and female double-heterozygous Smad3+/− db/m mice. Renal functions including urinary albumin excretion and serum creatinine were determined. Renal histological injury including renal fibrosis and inflammation were examined by periodic acid Schiff (PAS), periodic acid-silver methenamine (PASM), and immunohistochemistry (IHC) staining. Results Smad3 knockout (KO)-db/db mice were protected from the development of diabetic kidney injury, characterized by the normal levels of urinary albumin excretion and serum creatinine without any evidence for renal fibrosis and inflammation. In contrast, Smad3 wild-type (WT) db/db and Smad3+/− db/db mice developed progressively decline in renal function over the 12 to 32-week time course, including increased microalbuminuria and elevated levels of serum creatinine. Pathologically, Smad3 WT db/db and Smad3+/− db/db mice exhibited a marked deposition of collagen-I (col I), collagen-IV(col-IV), and an increased infiltration of F4/80+ macrophages in kidney. Mechanistically, Smad3 deficiency decreased the lncRNA Erbb4-IR transcription, while increased miR-29b transcription and therefore protected the kidney from progressive renal injury in db/db mice. Conclusion Results from this study imply that Smad3 may represent as a novel and effective therapeutic target for T2DN. |
| Databáze: | OpenAIRE |
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