MiRNA-337 leads to podocyte injury in mice with diabetic nephropathy
1Department of Nephrology, Beijing Chao-Yang Hospital of Capital Medical University, Beijing, China. 1274834875@qq.com.
Objective:
To elucidate the function of miRNA-337 in the pathogenesis of diabetic nephropathy (DN) and its underlying mechanism.
Materials And Methods:
Type 2 diabetes db/db mice were assigned into db/db group, vehicle group, and si-miR group, and age-matched db/m mice were in the db/m group. Differences in mouse serum glucose, body weight, serum creatinine, and albumin/creatinine ratio (ACR) among the four groups were compared at 6 weeks, 10 weeks, 14 weeks, 18 weeks, and 22 weeks of age. The expression level of miRNA-337 in mouse kidney tissues was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Correlation between miRNA-337 expression with ACR was analyzed. Through Western blot analysis, protein levels of interleukin 6 (IL-6), IL-18, podocin, nephrin, and desmin in mouse kidney tissues were detected.
Results:
With the increasing age, serum glucose, body weight, serum creatinine, and ACR in db/db mice gradually increased, which were remarkably higher than age-matched db/m mice. After treatment with miRNA-337 inhibitor in db/db mice, no remarkable changes in serum glucose and body weight were found, while serum creatinine and ACR decreased. Compared with db/m mice, miRNA-337 expression in kidney tissues of db/db mice upregulated, which was positively correlated with ACR. Expression levels of IL-6 and IL-18 in kidney tissues of db/db mice increased relative to db/m mice, but they were downregulated by miRNA-337 inhibitor treatment. Moreover, podocin and nephrin downregulated, while desmin upregulated in kidney tissues of db/db mice than db/m mice. By miRNA-337 inhibitor treatment in db/db mice, levels of podocin and nephrin increased, whereas desmin level decreased. We obtained similar results at their cellular level.
Conclusions:
We showed that miRNA-337 expression increases in db/db mice with diabetic nephropathy, which leads to podocyte injury by upregulating levels of IL-6 and IL-18.
Insights
MicroRNA-337 (miRNA-337) is upregulated in diabetic nephropathy (DN) and contributes to podocyte injury by increasing interleukin-6 and interleukin-18. Inhibiting miRNA-337 in mice with DN ameliorated kidney damage.
Area of Science:
- Biochemistry
- Molecular Biology
- Nephrology
Background:
- Diabetic nephropathy (DN) is a major complication of diabetes, characterized by progressive kidney damage.
- MicroRNAs (miRNAs) play crucial roles in the pathogenesis of various diseases, including DN.
- The specific role of miRNA-337 in DN remains to be fully elucidated.
Purpose of the Study:
- To investigate the function of miRNA-337 in the development of diabetic nephropathy (DN).
- To explore the underlying molecular mechanisms by which miRNA-337 influences DN pathogenesis.
- To assess the therapeutic potential of targeting miRNA-337 in DN.
Main Methods:
- Utilized type 2 diabetes db/db mice and age-matched db/m mice.
- Administered miRNA-337 inhibitor (si-miR) to db/db mice.
- Monitored serum glucose, body weight, serum creatinine, and albumin/creatinine ratio (ACR) over time.
- Quantified miRNA-337 expression in kidney tissues using qRT-PCR.
- Analyzed protein levels of IL-6, IL-18, podocin, nephrin, and desmin via Western blot.
Main Results:
- db/db mice exhibited elevated serum glucose, creatinine, and ACR compared to db/m mice.
- miRNA-337 expression was significantly upregulated in the kidneys of db/db mice and positively correlated with ACR.
- Treatment with a miRNA-337 inhibitor reduced serum creatinine and ACR in db/db mice.
- Kidney tissues of db/db mice showed increased IL-6 and IL-18, and decreased podocin and nephrin, with increased desmin.
- miRNA-337 inhibition reversed these changes, improving podocyte markers and reducing inflammatory cytokines.
Conclusions:
- miRNA-337 expression is elevated in diabetic nephropathy (DN).
- Increased miRNA-337 contributes to podocyte injury in DN by upregulating IL-6 and IL-18.
- Targeting miRNA-337 demonstrates therapeutic potential for DN treatment.
