Effects of dapagliflozin on renal fibrosis and TGF-β 1/p38MAPK pathway in type 2 diabetic nephropathy
10.3760/cma.j.cn341190-20240403-00338
- VernacularTitle:达格列净对2型糖尿病肾病肾纤维化及TGF-β 1/p38MAPK通路的影响
- Author:
Chen ZHANG
1
;
Lin NI
1
;
Yuefei SUN
1
Author Information
1. 湖州市第一人民医院内分泌科，湖州 313000
- Publication Type:Journal Article
- Keywords:
Diabetes mellitus, type 2;
Diabetic nephropathies;
Kidney;
Fibrosis;
Transforming growth factor beta1;
p38 Mitogen-activated protein kinases;
Blood glucose
- From:
Chinese Journal of Primary Medicine and Pharmacy
2025;32(1):7-13
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the therapeutic effects of dapagliflozin on renal fibrosis in patients with type 2 diabetic nephropathy (T2DN) and the underlying mechanisms involved.Methods:A randomized controlled study was conducted involving 152 patients with T2DN who received treatment at The First People's Hospital of Huzhou from April 2021 to May 2023. The patients were divided into an observation group and a control group, with 76 participants in each group, using a random number table method. The control group received conventional hypoglycemic therapy, while the observation group received dapagliflozin in addition to the conventional hypoglycemic therapy. Both groups were treated for 3 months. Before and after treatment, glycated hemoglobin, blood glucose, renal function indicators, and renal fibrosis markers (hyaluronic acid, type Ⅳ collagen, type Ⅲ procollagen, and laminin) were measured. Additionally, the levels of transforming growth factor-beta 1 (TGF-β 1), phosphorylated p38 mitogen-activated protein kinase (MAPK) pathway components [phosphorylated extracellular signal-regulated kinase (p-ERK),phosphorylated p38 mitogen-activated protein kinase (p-P38), phosphorylated c-Jun N-terminal Kinase (p-JNK)], and inflammatory factors (interleukin-6, interleukin-1 beta, and cyclooxygenase-2) in the patients' peripheral blood were measured. Transcriptome sequencing was performed to construct libraries and sequence the total RNA from kidney biopsy samples of the patients. Results:After treatment, the levels of hyaluronic acid, laminin, type Ⅳ collagen, and type Ⅲ procollagen in the observation group were (167.42 ± 17.91) μg/L, (106.10 ± 14.57) μg/L, (95.98 ± 10.03) μg/L, and (89.38 ± 9.75) μg/L, respectively. These values were significantly lower than those in the control group [(243.17 ± 24.38) μg/L, (147.43 ± 17.09) μg/L, (147.71 ± 14.59) μg/L, and (121.81 ± 14.88) μg/L, t = 21.83, 16.04, 25.47, 15.89, all P < 0.001]. The levels of interleukin-6, interleukin-1 beta, cyclooxygenase-2, TGF-β 1, and p-ERK, p-P38, and p-JNK in the observation group were significantly lower than those in the control group ( t = 9.45, 3.49, 11.30, 6.11, 4.26, 4.21, 2.04, all P < 0.05). Transcriptome sequencing enrichment analysis identified "fibronectin," "inflammatory response," and "TGF-β 1/P38 MAPK signaling pathway" as the differentially expressed signaling pathways. In kidney biopsy samples, the protein levels of TGF-β 1, p-ERK, and p-P38 in the observation group were (0.38 ± 0.15), (0.17 ± 0.10), and (0.58 ± 0.18), respectively, all of which were significantly lower than those in the control group [(0.16 ± 0.10), (0.07 ± 0.02), (0.19 ± 0.11), t = 2.99, 2.40, 4.53, all P < 0.05]. The overall response rate in the observation group was 93.43% (71/76), which was significantly higher than that in the control group [81.58% (62/76), χ2 = 7.02, P = 0.030]. Conclusions:Dapagliflozin has a beneficial therapeutic effect on renal fibrosis in patients with T2DN, as it can inhibit the expression of the TGF-β 1/p38 MAPK signaling pathway and reduce inflammation.
