Background: Lupus nephritis (LN) remains a major cause of morbidity and mortality in patients with systemic lupus erythematosus, and a substantial proportion of patients exhibit refractory disease despite standard immunosuppressive therapies. Increasing evidence suggests that aberrant cell–matrix interactions contribute to renal inflammation and fibrosis in LN [1]. Integrin α5 (ITGA5), a central mediator of extracellular matrix signaling, has been linked to tissue injury and fibrosis [2], yet its contribution to the pathogenesis of LN and therapeutic potential remain unclear.

Objectives: To determine whether ITGA5 contributes to lupus nephritis pathogenesis and whether the inhibition of ITGA5 improves renal outcomes in MRL/lpr mice.

Methods: The expression levels of ITGA5 in MRL/lpr mice and C57BL/6j were examined using Western blot, immunohistochemistry (IHC), and immunofluorescence(IF), respectively. 10-week-old MRL/lpr mice were treated with glucocorticoids, an ITGA5 inhibitor or vehicle control according to the experimental protocol. There were 6 mice in each treatment group. Renal function was assessed by serum creatinine and blood urea nitrogen (BUN) levels. Proteinuria was monitored longitudinally using standard quantitative assays. After 8 weeks of treatment, renal tissues were harvested for histopathological evaluation to assess the extent of kidney injury using H&E, PAS, and Masson staining. All procedures were conducted in accordance with institutional guidelines for animal care and use.

Results: Compared to C57BL/6j mouse, the levels of ITGA5 expression were increased in MRL/lpr mice. In the ITGA5 inhibitor- treated group, the levels of serum creatinine, BUN and 24h urine protein were significantly decreased compare to those treated with vehicle. For renal pathology assessment, mesangial expansion and glomerular endothelial cell injury were significantly lessened after the treatment with ITGA5 inhibitor.

Conclusions: This study demonstrated that pharmacological inhibition of ITGA5 confers significant renoprotective effects in MRL/lpr mice, further supporting ITGA5 as a promising non-immunosuppressive therapeutic target to ameliorate renal injury and preserve kidney function in lupus nephritis.

Figure 1.

The levels of ITGA5 expression were increased in MRL/lpr mice

Figure 2.

ITGA5 inhibitors improved laboratory parametersand renal histological alterations of MRL/lpr mice

REFERENCES: [1] Ramasamy A, Mohan C. Molecular and Cellular Mediators of Renal Fibrosis in Lupus Nephritis. International Journal of Molecular Sciences. 2025;26(6):2621.

[2] Li R, et al. Protective effects of macrophage-specific integrin α5 in inflammation and matrix interactions. Nature Communications. 2023;14:43369.

Acknowledgments: NIL.

Disclosure of Interests: None declared.