Background Macrophage infiltration is a hallmark of severe lupus nephritis, contributing to podocyte injury. Mesenchymal stem cell (MSC) transplantation could alleviate lupus nephritis in both lupus mice and patients. However, the underlying mechanisms remain largely unknown.
Objectives The study was designed to investigate the modulatory effect of MSCs on macrophage polarization and explore its role in preventing podocyte injury.
Methods B6.MRL-Faslpr (B6.lpr) mice were injected with umbilical cord MSCs (UCMSCs), while the control groups were administered with PBS or Fibroblasts. A 24-hour urine specimen was collected by putting mice in metabolic cages over a full 24-hour period every three weeks. 9 weeks later, all the mice were sacrificed. Histopathology scores of kidney were evaluated by hematoxylin-eosin (HE) staining. IgG and C3 deposits in glomeruli were assessed by immunofluorescence. Podocyte foot processes were observed under the transmission electron microscope. Mouse peritoneal macrophages were co-cultured with or without UCMSCs for 2 days, and further co-cultured with mouse podocytes for another 2 days. The expression of TNF-α, MCP-1, IL-1β and CD206 in macrophages and synaptopodin in podocytes were determined by real-time PCR. Flow cytometry was used to analyze podocyte apoptosis.
Results UCMSCs treated B6.lpr mice showed lower levels of proteinuria, reduced glomerular deposition of IgG and C3, decreased renal histopathology scores and less foot process fusion. Besides, UCMSCs decreased macrophages infiltration while increased the expression of CD206 and synaptopodin in the kidney of B6.lpr mice. In vitro study demonstrated that macrophages co-cultured with UCMSCs expressed lower levels of inflammatory cytokines including TNF-α, MCP-1 and IL-1β, while higher levels of CD206. Moreover, UCMSCs treated macrophages induced less podocyte injury, with higher expression of synaptopodin and lower apoptotic rate.
Conclusions UCMSCs prevented podocyte injury in lupus nephritis via educating macrophage into an anti-inflammatory phenotype, thus rescuing renal function.
Disclosure of Interest None declared
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