Podocyte-Specific Deletion of MCP-1 Fails to Protect against Angiotensin II- or Adriamycin-Induced Glomerular Disease

• Published in: International journal of molecular sciences Vol. 25; no. 9; p. 4987
• Main Authors: Bondi, Corry D, Hartman, Hannah L, Rush, Brittney M, Tan, Roderick J
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.05.2024
• Subjects: Angiotensin II; Animals; Anthracyclines; CCL2; CCR2; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Chemokines; chronic kidney disease; Chronic kidney failure; Diabetes; Disease Models, Animal; Doxorubicin - adverse effects; Gene Deletion; glomerular injury; Kidneys; Male; Medical research; Medicine, Experimental; Mice; Mice, Knockout; podocyte; Podocytes - drug effects; Podocytes - metabolism; Podocytes - pathology; Proteins; proteinuria; Renal Insufficiency, Chronic - chemically induced; Renal Insufficiency, Chronic - genetics; Renal Insufficiency, Chronic - metabolism; Renal Insufficiency, Chronic - pathology; Survival analysis; CCL2; chronic kidney disease; glomerular injury; proteinuria; podocyte; CCR2
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25094987

Investigating the role of podocytes in proteinuric disease is imperative to address the increasing global burden of chronic kidney disease (CKD). Studies strongly implicate increased levels of monocyte chemoattractant protein-1 (MCP-1/CCL2) in proteinuric CKD. Since podocytes express the receptor for MCP-1 (i.e., CCR2), we hypothesized that podocyte-specific MCP-1 production in response to stimuli could activate its receptor in an autocrine manner, leading to further podocyte injury. To test this hypothesis, we generated podocyte-specific MCP-1 knockout mice (Podo- ) and exposed them to proteinuric injury induced by either angiotensin II (Ang II; 1.5 mg/kg/d, osmotic minipump) or Adriamycin (Adr; 18 mg/kg, intravenous bolus). At baseline, there were no between-group differences in body weight, histology, albuminuria, and podocyte markers. After 28 days, there were no between-group differences in survival, change in body weight, albuminuria, kidney function, glomerular injury, and tubulointerstitial fibrosis. The lack of protection in the knockout mice suggests that podocyte-specific MCP-1 production is not a major contributor to either Ang II- or Adr-induced glomerular disease, implicating that another cell type is the source of pathogenic MCP-1 production in CKD.