Dual blockade of DPP-4 and CXCL12/CXCR4 axes synergistically protects podocytes in lupus nephritis.

ABSTRACT:

Background

Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), is characterized by podocyte injury that contributes to disease progression. Dipeptidyl peptidase-4 (DPP-4) inhibitors, though developed for diabetes, have shown renoprotective potential. However, DPP-4 inhibition may elevate CXCL12/CXCR4 signaling, a pathway implicated in LN pathogenesis. This study aimed to determine whether dual DPP-4 and CXCL12/CXCR4 blockade confers enhanced renal protection in LN.

Methods

MRL/lpr lupus-prone mice were treated with the DPP-4 inhibitor linagliptin, either alone or in combination with the CXCL12/CXCR4 axis antagonist AMD3100. We evaluated renal function, histopathology, podocyte structure, and markers of oxidative stress, fibrosis, and inflammati

SUBMITTER: Hu HM 

PROVIDER: S-EPMC12832377 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature