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Oridonin ameliorates renal fibrosis in diabetic nephropathy by inhibiting the Wnt/β-catenin signaling pathway.
- Source :
-
Renal failure [Ren Fail] 2024 Dec; Vol. 46 (1), pp. 2347462. Date of Electronic Publication: 2024 Jun 04. - Publication Year :
- 2024
-
Abstract
- Diabetic nephropathy (DN) is one of the most serious and frequent complications among diabetes patients and presently constitutes vast the cases of end-stage renal disease worldwide. Tubulointerstitial fibrosis is a crucial factor related to the occurrence and progression of DN. Oridonin (Ori) is a diterpenoid derived from rubescens that has diverse pharmacological properties. Our previous study showed that Ori can protect against DN by decreasing the inflammatory response. However, whether Ori can alleviate renal fibrosis in DN remains unknown. Here, we investigated the mechanism through which Ori affects the Wnt/β-catenin signaling pathway in diabetic rats and human proximal tubular epithelial cells (HK-2) exposed to high glucose (HG) levels. Our results revealed that Ori treatment markedly decreased urinary protein excretion levels, improved renal function and alleviated renal fibrosis in diabetic rats. In vitro , HG treatment increased the migration of HK-2 cells while reducing their viability and proliferation rate, and treatment with Ori reversed these changes. Additionally, the knockdown of β-catenin arrested cell migration and reduced the expression levels of Wnt/β-catenin signaling-related molecules (Wnt4, p-GSK3β and β-catenin) and fibrosis-related molecules (α-smooth muscle actin, collagen I and fibronectin), and Ori treatment exerted an effect similar to that observed after the knockdown of β-catenin. Furthermore, the combination of Ori treatment and β-catenin downregulation exerted more pronounced biological effects than treatment alone. These findings may provide the first line of evidence showing that Ori alleviates fibrosis in DN by inhibiting the Wnt/β-catenin signaling pathway and thereby reveal a novel therapeutic avenue for treating tubulointerstitial fibrosis.
- Subjects :
- Animals
Humans
Male
Rats
beta Catenin metabolism
Cell Line
Cell Movement drug effects
Cell Proliferation drug effects
Kidney pathology
Kidney drug effects
Kidney Tubules, Proximal drug effects
Kidney Tubules, Proximal pathology
Kidney Tubules, Proximal metabolism
Rats, Sprague-Dawley
Diabetes Mellitus, Experimental complications
Diabetes Mellitus, Experimental drug therapy
Diabetic Nephropathies drug therapy
Diabetic Nephropathies metabolism
Diabetic Nephropathies etiology
Diterpenes, Kaurane pharmacology
Diterpenes, Kaurane therapeutic use
Fibrosis drug therapy
Wnt Signaling Pathway drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1525-6049
- Volume :
- 46
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Renal failure
- Publication Type :
- Academic Journal
- Accession number :
- 38832497
- Full Text :
- https://doi.org/10.1080/0886022X.2024.2347462