Tubular Epithelia-Specific Deletion of MCP-1 Does Not Afford Protection Against Adriamycin-Induced Kidney Injury

TL;DR

Deleting MCP-1 in kidney tubular cells does not protect against Adriamycin-induced kidney damage in mice.

Contribution

Shows that tubule-specific MCP-1 deletion does not prevent Adriamycin-induced kidney injury in mice.

Findings

MCP-1 deletion in tubular cells reduced Mcp-1 transcript and protein levels.

KO mice showed no difference in survival, albuminuria, or kidney injury compared to controls.

Tubule-secreted MCP-1 is not essential for Adriamycin-induced kidney injury progression.

Abstract

The increasing global burden of chronic kidney disease (CKD) magnifies an urgent need to find treatable targets. Monocyte chemoattractant protein-1 (MCP-1/CCL2) is a chemokine secreted by kidney tubular epithelia in response to a variety of stimuli. To better understand the effects of tubular MCP-1 in response to kidney injury, we generated tubular epithelia-specific MCP-1 knockout mice (KO; Pax8-Mcp-1fl/fl). We then exposed these mice and their control littermates to Adriamycin (Adr; 18 mg/kg, IV bolus). Thirty-two days after Adr injection, Mcp-1 transcript and protein levels were suppressed in the KO mice compared to their wild-type (WT) littermates. The KO mice exhibited no effect on survival, change in body weight, albuminuria, kidney function, glomerular or tubular injury, or tubulointerstitial fibrosis compared to WT. Overall, the results suggest that tubule-secreted MCP-1 is not necessary for progression of Adr-induced injury. These findings contribute to our understanding of the role of MCP-1 in kidney injury.

Figures