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Renal disease is caused by tubular interstitial injury and renal interstitial fibrosis. Previous studies have shown that transplantation of endothelial progenitor cells (EPCs) may provide an appropriate treatment for repair and reversing renal pathology. However, EPCs are typically low in abundance and have poor replication ability. Therefore, the this study investigated the use of EPCs transfected with the telomerase reverse transcriptase (TERT) in rats that had undergone five out of six subtotal nephrectomy. This study determined the effects of EPC transplantation on renal function, renal interstitial fibrosis, and peritubular capillary angiogenesis. Five groups of rats were investigated: sham group, model group (five out of six subtotal nephrectomy), EPCs-N group (transplantation with EPCs), pZ-TERT-EPCs-N group (transplantation with EPCs transfected with TERT), and pZ-EPCs-N group (transplantation with EPCs transfected with empty plasmid). At weeks 4, 8, and 12 after transplantation, renal function, renal interstitial fibrosis, and peritubular microvessel density (MVD) were investigated. EPCs transfected with TERT gene showed decreased in vitro senescence, apoptosis, and proliferative ability was significantly enhanced (p < 0.05). Furthermore, rat transplanted with EPCs transfected with TERT showed significantly reduced renal interstitial fibrosis and increased endogenous creatinine clearance rate and peritubular MVD (p < 0.05). The transplantation of EPCs expressing TERT into five out of six subtotal nephrectomy rats was shown to improve renal function, reduce loss of peritubular microvessel, and inhibit progression of renal interstitial fibrosis. These studies provide the basis for a potential treatment of renal disease using genetically modified EPCs.

Plasmacytoid dendritic cells (pDCs) play a key role in the initiation and amplification of systemic lupus erythematosus (SLE)‐associated vascular injury. In this study, we found that dsDNA induced dose‐ and time‐dependent increase in IFN‐α and Toll‐like receptor 7 (TLR7), TLR9 and IRF7 expression in pDCs. Co‐cultured circulating endothelial cells (ECs) with activated pDCs significantly decreased proliferation, tube formation and migration in ECs. The elevated level of cellular IFN‐α increased cell adhesion, promoted cell apoptosis, induced cell senescence and arrested cells at G0/G1 phase of endothelial progenitor cells (EPCs). Additionally, the co‐culture system activated MAPK and inactivated PI3K. Pristane was used to establish a in vivo SLE‐like mouse model. Importantly, we showed that INF‐α‐neutralizing antibody (IFN‐α‐NA) rescued all the changes induced by IFN‐α in vitro and prevented vascular injury in pristane‐induced SLE model in vivo. In conclusion, we confirmed that activated pDCs promoted vascular damage and the dysfunction of ECs/EPCs via IFN‐α production. IFN‐α‐neutralizing antibody may be a clinical implication for preventing vascular injury. PI3K signalling and AMPK signalling were associated with SLE‐associated vascular functions. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease including the cardiovascular system. Atherosclerosis is the most common cardiovascular complication of SLE and a significant risk factor for morbidity and mortality. Vascular damage/protection mechanism in SLE patients is out of balance, caused by the cascade reaction among oxidative stress, proinflammatory cytokines, Neutrophil Extracellular Traps, activation of B cells and autoantibodies and abnormal T cells. As a precursor cell repairing vascular endothelium, endothelial progenitor cells (EPCs) belong to the protective mechanism and show the reduced number and impaired function in SLE. However, the pathological mechanism of EPCs dysfunction in SLE remains ill-defined. This paper reviews the latest SLE epidemiology and pathogenesis, discusses the changes in the number and function of EPCs in SLE, expounds the role of EPCs in SLE atherosclerosis, and provides new guidance and theoretical basis for exploring novel targets for SLE treatment. [ABSTRACT FROM AUTHOR]