| First Author | Chang TT | Year | 2023 |
| Journal | Biomed Pharmacother | Volume | 161 |
| Pages | 114450 | PubMed ID | 36863097 |
| Mgi Jnum | J:346348 | Mgi Id | MGI:7448063 |
| Doi | 10.1016/j.biopha.2023.114450 | Citation | Chang TT, et al. (2023) Macrophage inflammatory protein-1beta as a novel therapeutic target for renal protection in diabetic kidney disease. Biomed Pharmacother 161:114450 |
| abstractText | Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide and the prevalence of DKD has increased over recent decades. Inflammation is involved in the development and progression of DKD. In this study, we explored the potential role of macrophage inflammatory protein-1beta (MIP-1beta) in DKD. Clinical non-diabetic subjects and DKD patients with different levels of urine albumin-to-creatinine ratio (ACR) were enrolled in the study. Lepr(db)/(db) mice and MIP-1beta knockout mice were also used as mouse models for DKD. We found that serum MIP-1beta levels were elevated in the DKD patients, especially those with ACRs that were less than or equal to 300, suggesting that MIP-1beta is activated in clinical DKD. The administration of anti-MIP-1beta antibodies attenuated DKD severity in the Lepr(db)/(db) mice, which also showed reduced glomerular hypertrophy and podocyte injury, as well as decreased inflammation and fibrosis, suggesting that MIP-1beta plays a role in the development of DKD. The MIP-1beta knockout mice showed improved renal function and decreased renal glomerulosclerosis and fibrosis in DKD. Furthermore, podocytes from the MIP-1beta knockout mice showed less high glucose-induced inflammation and fibrosis compared to those from wild-type mice. In conclusion, the inhibition or deletion of MIP-1beta protected podocytes, modulated renal inflammation, and ameliorated experimental DKD, suggesting that novel anti-MIP-1beta strategies could potentially be used to treat DKD. |
