Macrophages communicate with mesangial cells through the CXCL12/DPP4 axis in lupus nephritis pathogenesis.
Cell Death Dis
; 15(5): 344, 2024 May 18.
Article
in En
| MEDLINE
| ID: mdl-38762508
ABSTRACT
Lupus nephritis (LN) occurs in 50% of cases of systemic lupus erythematosus (SLE) and is one of the most serious complications that can occur during lupus progression. Mesangial cells (MCs) are intrinsic cells in the kidney that can regulate capillary blood flow, phagocytose apoptotic cells, and secrete vasoactive substances and growth factors. Previous studies have shown that various types of inflammatory cells can activate MCs for hyperproliferation, leading to disruption of the filtration barrier and impairment of renal function in LN. Here, we characterized the heterogeneity of kidney cells of LN mice by single-nucleus RNA sequencing (snRNA-seq) and revealed the interaction between macrophages and MCs through the CXC motif chemokine ligand 12 (CXCL12)/dipeptidyl peptidase 4 (DPP4) axis. In culture, macrophages modulated the proliferation and migration of MCs through this ligand-receptor interaction. In LN mice, treatment with linagliptin, a DPP4 inhibitor, effectively inhibited MC proliferation and reduced urinary protein levels. Together, our findings indicated that targeting the CXCL12/DPP4 axis with linagliptin treatment may serve as a novel strategy for the treatment of LN via the CXCL12/DPP4 axis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lupus Nephritis
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Dipeptidyl Peptidase 4
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Cell Proliferation
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Mesangial Cells
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Chemokine CXCL12
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Macrophages
Limits:
Animals
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Female
/
Humans
Language:
En
Journal:
Cell Death Dis
Year:
2024
Document type:
Article
Affiliation country:
China