Related Experiment Video
Updated: Jun 21, 2026

Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity
Published on: June 7, 2017
Macrophage Depletion Alleviates Immunosenescence in Diabetic Kidney by Modulating GDF-15 and Klotho
Asma S Alonazi1, Rana M Aloraini1, Lama M Albulayhi1
1Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Abstract:
Cellular senescence is a hallmark of aging and contributes to age-related diseases, including diabetic nephropathy (DN). Additionally, macrophage-mediated inflammation has been linked with DKD. Therefore, we investigated the effect of macrophage depletion on kidney cell senescence in DN, focusing on the relationship between the GDF-15 and Klotho signaling pathways. Wistar albino rats (n = 24) were divided into four groups: healthy control, liposomal clodronate (LC)-treated healthy, diabetic, and LC-treated diabetic groups. Rats in the LC-treated healthy, diabetic, and LC-treated diabetic groups were intravenously administered LC once a week for 4 weeks. Rat models of type 2 diabetes were successfully established via the administration of streptozotocin and a high-fat diet, as evidenced by increased blood glucose levels, kidney weight to body weight (KW/BW) ratio, serum albumin, creatinine, and urea levels, kidney damage, and oxidative stress. However, LC-mediated macrophage depletion reduced the KW/BW ratio, improved serum and oxidative parameters, decreased inflammatory markers (IL-6 and TNF-α), and ameliorated oxidative stress. Additionally, LC treatment promoted macrophage polarization towards the anti-inflammatory phenotype, downregulated GDF-15 expression, upregulated Klotho expression, and ameliorated kidney damage. In conclusion, macrophage depletion combats kidney senescence by modulating Klotho and GDF-15, indicating their potential as novel targets in DN treatment.
Related Concept Videos
Glucose Transporters
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
Glucose Absorption Into the Small Intestine
Hormones Regulating Blood Glucose
In addition to accelerating glucose uptake and utilization, insulin has...
Type I Diabetes II: Pathophysiology
Type II Diabetes II: Pathophysiology
Diabetic Nephropathy

