Macrophage inflammatory protein-1β as a novel therapeutic target for renal protection in diabetic kidney disease

Ting-Ting Chang; Szu-Yuan Li; Liang-Yu Lin; Ching Chen; Jaw-Wen Chen

doi:10.1016/j.biopha.2023.114450

Macrophage inflammatory protein-1β as a novel therapeutic target for renal protection in diabetic kidney disease

Biomed Pharmacother. 2023 May:161:114450. doi: 10.1016/j.biopha.2023.114450. Epub 2023 Feb 28.

Authors

Ting-Ting Chang¹, Szu-Yuan Li², Liang-Yu Lin³, Ching Chen⁴, Jaw-Wen Chen⁵

Affiliations

¹ Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: tf0619@nycu.edu.tw.
² School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
³ School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
⁴ Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁵ Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: jwchen@vghtpe.gov.tw.

PMID: 36863097
DOI: 10.1016/j.biopha.2023.114450

Abstract

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-1β (MIP-1β) 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-1β knockout mice were also used as mouse models for DKD. We found that serum MIP-1β levels were elevated in the DKD patients, especially those with ACRs that were less than or equal to 300, suggesting that MIP-1β is activated in clinical DKD. The administration of anti-MIP-1β 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-1β plays a role in the development of DKD. The MIP-1β knockout mice showed improved renal function and decreased renal glomerulosclerosis and fibrosis in DKD. Furthermore, podocytes from the MIP-1β 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-1β protected podocytes, modulated renal inflammation, and ameliorated experimental DKD, suggesting that novel anti-MIP-1β strategies could potentially be used to treat DKD.

Keywords: Chemokine; Diabetic kidney disease; Inflammation; Macrophage inflammatory protein-1β; Podocyte.

MeSH terms

Animals
Diabetes Mellitus* / pathology
Diabetic Nephropathies* / pathology
Fibrosis
Inflammation / pathology
Kidney / pathology
Kidney / physiology
Mice
Mice, Knockout
Podocytes*

Substances

Ccl4 protein, mouse