As systemic lupus erythematosus (SLE) primarily impacts women of childbearing age, a considerable number of patients have fertility needs. However, the risk of experiencing adverse pregnancy outcomes (APOs) was higher in these patients. Our study aimed to construct a predictive model to assess the risks for APOs of SLE. We retrospectively analyzed the data of pregnant SLE patients hospitalized at Nanjing Drum Tower Hospital from August 2010 to April 2023. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was used to explore the risk factors for APOs, and a nomogram was established. Afterward, the efficacy of the nomogram was evaluated by analyzing the areas under the curves (AUCs) of Receiver Operating Characteristic (ROC), calibration curves, and Decision Curve Analysis (DCA). Our study involved 259 pregnant patients with a median age of 29.00 years, and identified 129 cases of APOs, including preterm birth, low birth weight, congenital anomalies, stillbirth/miscarriage, and fetal distress. Through LASSO regression analysis, nine optimal features were selected as risk factors, including age, lupus nephritis, antepartum body mass index, antinuclear antibody, anti-U1RNP/Sm antibody, anti-ribosomal P protein antibody, platelet, albumin levels, SLEDAI scores, diabetes mellitus, rash, and the use of aspirin therapy. These factors were integrated into a predictive nomogram model, which showed good predictive accuracy, with AUC values of 0.870 and 0.830 in training and validation groups, respectively. The calibration curves and DCA also confirmed the good performance of the model. We developed a tool to predict APOs in SLE patients, offering personalized risk assessments and clinical decision support. As the data used to build the predictive model was obtained from a single center, the tool is currently best suited for application within our center. Further validation in diverse populations is needed to expand its generalizability.

ObjectiveNeutrophil extracellular traps (NETs) have been implicated in rheumatoid arthritis (RA) pathogenesis, yet their effects on fibroblast-like synoviocytes (FLS) remain unclear. This study aims to investigate the role of NETs in RA FLS migration, proliferation, and invasion, as well as the underlying molecular mechanisms.MethodsNETs formation was assessed in neutrophils isolated from RA patients and healthy controls (HC) using immunofluorescence staining. RA FLS were stimulated by RA or HC derived NETs, and migration was evaluated via wound healing assays. RNA sequencing (RNA-seq) identified differentially expressed genes in FLS, validated by qPCR. The expression and localization of glycoprotein Ib alpha (GPIbα) in RA synovium were examined by immunohistochemistry. GPIbα was knocked down in FLS to assess its role in proliferation and migration. A collagen-induced arthritis (CIA) model was used to study the effect of NETs inhibition on RA progression.ResultsRA neutrophils produced more NETs than HC neutrophils. RA NETs enhanced FLS migration and proliferation, and RNA-seq revealed upregulation of GP1BA, which was confirmed by qPCR. GPIbα expression was elevated in RA synovium. GP1BA knockdown suppressed RA NETs-induced FLS proliferation and migration. In CIA mice, inhibiting NETs formation decreased GPIbα expression, limited FLS invasiveness, and attenuated RA progression.ConclusionOur findings reveal that NETs promote RA progression by inducing FLS proliferation and migration through GPIbα. Consequently, targeting NETs formation or GPIbα represents a promising therapeutic strategy to mitigate RA.

Breast cancer stem cells (BCSCs) are recognized as a critical subpopulation involved in cancer recurrence and metastasis, as they are capable of self-renewal and differentiate into various cell types. BCSCs play significant roles in tumor progression, being regulated by key signaling pathways such as Notch, PI3K/AKT/mTOR, and Hedgehog, and their interactions with the tumor microenvironment, which affect tumor growth and resistance to therapeutics. This review focuses on the surface markers of BCSCs, their roles in recurrence and metastasis, and the key signaling pathways. It also discusses the recent progress in understanding how BCSCs contribute to drug resistance and explores potential therapeutic strategies targeting these cells and their microenvironment to improve clinical outcomes and prevent relapse.

Background Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been used to estimate disease activity in many diseases. Our study aims to determine the role of NLR and PLR in evaluating vasculitis activity and specific organ involvement in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). Methods We retrospectively reviewed the medical records of 81 AAV patients. Clinical characteristics, laboratory investigations and Birmingham vasculitis activity score (BVAS) were collected. Correlation analysis was performed between NLR/PLR and BVAS. Receiver operating characteristic (ROC) curve was calculated for differentiating organ involvement. Results Both NLR and PLR were positively correlated with BVAS in AAV patients. AAV patients with pulmonary, cardiac or renal involvement exhibited higher levels of NLR and PLR than those without pulmonary, cardiac or renal involvement. Notably, area under curves (AUC) of NLR and PLR for differentiating cardiac involvement were 0.79 (95% CI: 0.53–0.95) and 0.77 (95% CI: 0.49–0.94), respectively. Conclusions NLR and PLR showed favorable performance in accessing vasculitis activity and specific organ involvement in AAV patients.

BACKGROUND:Ubiquitin-mediated degradation of the Mas-related G protein-coupled receptor C (MrgC) reduces the number of receptors. However, the specific deubiquitinating enzyme antagonize this process has not been reported. In this study, we investigated the effect of ubiquitin-specific protease-48 (USP48) on bone cancer pain (BCP) and its effect on MrgC.METHODS:A mouse model of BCP was established. BCP behaviours of mice were assessed after intrathecal injection of adeno-associated virus (AAV)-USP48. USP48 and MrgC interactions were studied by immunoprecipitation. Overexpression and knockdown of USP48 were conducted in N2a cells to investigate the effect of USP48 on MrgC receptor number and ubiquitination.RESULTS:Spinal cord level USP48 expression was reduced in mice with BCP. Intrathecal injection of AAV-USP48 increased paw withdrawal mechanical threshold and reduced spontaneous flinching in mice. In N2a cells, there were increased number of MrgC receptors after overexpression of USP48 and decreased number of MrgC receptors after knockdown of USP48. USP48 interacted with MrgC and overexpression of USP48 altered the level of ubiquitination of MrgC.CONCLUSION:USP48 antagonizes ubiquitin-mediated autophagic degradation of MrgC and alleviates BCP in a murine animal model. Our findings may provide a new perspective for the treatment of BCP.SIGNIFICANCE:Our finding may provide an important theoretical basis as well as an intervention target for clinical development of drugs for BCP.

Objective. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been used to estimate disease activity in many diseases. However, the analysis of NLR and PLR in patients with ANCA-associated vasculitis (AAV) has not yet been performed. Our study aims to determine the role of NLR and PLR in evaluating vasculitis activity and specific organ involvement in AAV.Methods. We retrospectively reviewed the medical records of 81 AAV patients. Clinical characteristics, laboratory investigations and Birmingham vasculitis activity score (BVAS) were collected. Correlation analysis was performed between NLR/PLR and BVAS. Receiver operating characteristic (ROC) curve was calculated for differentiating organ involvement.Results. Both NLR and PLR were positively correlated with BVAS in AAV patients. Patients with pulmonary (7.00 ± 0.70), cardiac (16.30 ± 4.71) or renal (7.19 ± 0.74) involvement exhibited higher levels of NLR than those without pulmonary (4.38 ± 0.89, P=0.04), cardiac (6.02 ± 0.52, P=0.02) or renal (4.41 ± 0.94, P=0.03) involvement respectively. Patients with pulmonary (244.6 ± 17.41), cardiac (401.6 ± 77.75) or renal (251.6 ± 18.20) involvement also exhibited higher levels of PLR than those without pulmonary (141.0 ± 22.81, P=0.003), cardiac (222.3 ± 15.70, P=0.03) or renal (143.7 ± 20.32, P=0.0004) involvement respectively. A cut-off level of 8.22 for NLR had 83% sensitivity and 80% specificity to predict cardiac involvement.Conclusion. NLR and PLR showed favorable performance in accessing vasculitis activity and specific organ involvement in AAV patients.

Systemic lupus erythematosus (SLE) patients exist an imbalance between regulatory T (Treg) and T helper 17 cells (Th17), which might be contributed by defective immune regulation of bone marrow derived mesenchymal stem cells (BM-MSCs) from SLE patients. Our microRNA array analysis showed markedly down-regulated expression levels of microRNA let-7f in BM-MSCs from SLE patients compared to those from normal controls (NOR). To explore the role of let-7f in the disease pathogenesis, we showed that expression levels of let-7f in SLE BM-MSCs were negatively associated with SLE disease activity, and the predicted let-7 family targeted gene expression of interlukin-6 (IL-6) was significantly higher in BM-MSCs from SLE patients compared to normal controls (NOR). Transient transfection of BM-MSCs with let-7f mimics or inhibitors showed reduced levels of let-7f impaired the proliferation rate of BM-MSCs, BM-MSC-mediated downregulation of Th17 cells and upregulation of Treg cells, increased the apoptosis rate of BM-MSCs through targeting IL-6 and activating signal transducers and activators of transcription-3 (STAT3) pathway, but had no significant effect on the differentiation of Th1 and Th2. Our findings showed a key role of let-7f in the imbalance of Treg/Th17 mediated by SLE BM-MSCs, suggesting the potential of manipulating let-7f expression in BM-MSCs for treating SLE patients.

Bone marrow mesenchymal stem cells (BMSC) have been shown to possess immunomodulatory activities, while its role in rheumatoid arthritis (RA) remains unknown. Citrullinated fibrinogen (cfb) has been considered as a specific autoantigen in RA pathogenesis. Our study aims to determine the role of cfb on immunomodulatory function of BMSC. We demonstrated the specific role of toll-like receptor 4 (TLR4)-NFκB pathway in the pro-inflammatory response of BMSC to cfb with increased production of interleukin (IL)-6, IL-8 and chemokine CC motif ligand 2 (CCL2). Moreover, cfb impaired BMSC-mediated suppression of peripheral blood mononuclear cells (PBMC) proliferation and reduced the production of the key immunomodulatory molecule indoleamine 2,3-dioxygenase (IDO) in BMSC. We have uncovered a previously unrecognized role of cfb in interfering BMSC-mediated immunoregulation in RA. Cfb could act as a damage-associated molecule pattern (DAMP) for BMSC and thereby contribute to the propagation of inflammation in RA.

Patients with systemic lupus erythematosus (SLE) have a tremendously increased risk for cardiovascular disease (CVD), which could not be accounted in entirety by traditional Framingham risk factors. To study whether the accelerated atherosclerosis in SLE patients is mediated by type I interferon (IFN-I) through the regulation of endothelial progenitor cells (EPCs), we created a line of C57BL/6 mice with deficiency in both apolipoprotein E (ApoE−/−) and fas ligand (FasL−/−, gld.). As expected, the resultant gld. ApoE−/− mice exhibited both aggravated lupus-like disease and atherosclerosis under normal diet. Increased expression of IFN-I-stimulated genes (ISGs) was closely associated with depletion and dysfunction of EPCs, as well as with accelerated atherosclerotic lesion in gld. ApoE−/− mice. While only IFN-α instead of other interventions, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IRS423 and IRS661, impaired EPC function in vitro. Mechanistically, activation or inhibition of the TLR7/9 signaling could modulate EPC number and function in vivo. Decreased proliferation rate and increased apoptotic rate of EPCs induced by IFN-α might contribute to the results to a certain extent. Thus, our data suggest that excessive expression of IFN-I through the activation of TLR7/9 signaling may induce accelerated atherosclerosis in lupus through the depletion or dysfunction of EPCs, suggesting that targeting IFN-I might have potential therapeutic effects on both lupus disease and premature atherosclerosis in SLE patients.

Caloric restriction (CR) increases lifespan, retards physiological signs of aging, and delays a variety of diseases. Reduction of inflammatory response was proposed as one of the molecular mechanisms for how CR exerts beneficial effects. The present study investigated the effects of CR on postoperative pain in rats. Adult nonobese rats were divided into two dietary groups, an ad libitum fed group (AL) and a caloric restriction group (CR) that was provided with 60% of the food intake of AL rats. After 6 weeks, the effects of CR on pain behaviors and inflammation induced by plantar incision were examined. CR rats displayed significantly reduced nonevoked pain, mechanical allodynia and thermal hyperalgesia induced by incision, and showed decreased levels of pro-inflammatory cytokines in serum, peri-incisional skin tissue and ipsilateral spinal cord dorsal horn at 6 h and 24 h after incision. The analgesic efficiency of parecoxib and morphine, two agents widely used for the management of postoperative pain clinically, was reinforced by CR. Together, CR generates antinociceptive effects on postoperative incisional pain in rats, perhaps providing some improvement of QOL in patients with postoperative pain, and the beneficial effects may be attributable to the inhibition of excessive inflammation induced by surgical injury.

Excessive inflammatory responses play important roles in the aggravation of secondary damage to an injured spinal cord. Dexmedetomidine (DEX), a selective α2-adrenoceptor agonist, has recently been implied to be neuroprotective in clinical anesthesia, but the underlying mechanism is elusive. As signaling through Toll-like receptor 4 (TLR4) and nicotinic receptors (nAChRs, notably α7nAChR) play important roles in the pro- and anti-inflammation systems in the central nervous system, respectively, this study investigated whether and how they were modulated by DEX pretreatment in a rat model of spinal cord compression. The model was used to mimic perioperative compressive spinal cord injury (SCI) during spinal correction. DEX preconditioning improved locomotor scores after SCI, which was accompanied by increased α7nAChR and acetylcholine (Ach, an endogenous ligand of α7nAChR) expression as well as PI3K/Akt activation. However, there was a decrease in Ly6h (a negative regulator for α7nAChR trafficking), TLR4, PU.1 (a critical transcriptional regulator of TLR4), HMGB1 (an endogenous ligand of TLR4), and caspase 3-positive cells, which was prevented by intrathecal preconditioning with antagonists of either α2R, α7nAChR or PI3K/Akt. In addition, application of an α7nAChR agonist produced effects similar to those of DEX after SCI, while application of an α7nAChR antagonist reversed these effects. Furthermore, both α7nAChR and TLR4 were mainly co-expressed in NeuN-positive cells of the spinal ventral horn, but not in microglia or astrocytes after SCI. These findings imply that the α2R/PI3K/Akt/Ly6h and α7nAChR/PI3K/Akt/PU.1 cascades are required for upregulated α7nAChR and downregulated TLR4 expression by DEX pretreatment, respectively, which provided a unique insight into understanding DEX-mediated neuroprotection.

Treatment of remifentanil-induced postoperative hyperalgesia (RIH) remains a clinical challenge because the mechanisms are not fully understood. Matrix metalloproteinase-9 (MMP-9) is a key component in neuroinflammation because of its facilitation of pro-inflammatory cytokine maturation. Therefore, inhibition of MMP-9 may represent a novel therapeutic approach to the treatment of RIH. Sprague-Dawley rats were randomly divided into three groups: Control, Incision and Remifentanil. A right plantar surgical incision was performed in Group Incision, and intraoperative remifentanil (0.04 mg/kg, 0.4 ml) was infused subcutaneously for 30 min in Group Remifentanil. The results indicated that intraoperative remifentanil induced an up-regulation and activation of MMP-9 in DRGs but not spinal cords. MMP-9 was expressed primarily in DRG neurons co-expressing mu opioid receptors (MOR), and elicited interleukin-1β (IL-1β) cleavage in DRG neurons and satellite glial cells (SGCs). Intraperitoneal injection of N-acetyl-cysteine (NAC), a broadly used safe drug, significantly attenuated RIH via suppressing the activation of MMP-9 in DRGs. NAC inhibited the cleavage of IL-1β in DRGs, which is a critical substrate of MMP-9, and markedly suppressed glial activation and neuron excitability in spinal dorsal horn induced by remifentanil. These results demonstrated that NAC can effectively alleviate RIH via powerfully inhibiting MMP-9 activation in DRGs.

Systemic lupus erythematosus (SLE) is an autoimmune disease manifested by multiorgan impairment. It is reported that B cells participate in the onset of SLE. Bruton’s tyrosine kinase (Btk), as a downstream signaling molecule of B cell antigen receptor (BCR) signaling pathway, is involved in the development, activation, and survival of B cells. The aim of our study was to explore the specific role of Btk in lupus nephritis (LN). We determined the percentages of Btk+ B cells in peripheral blood mononuclear cells (PBMCs) from SLE patients by flow cytometry and analyzed the correlation between the percentage of Btk+ B cells and lupus-related clinical indexes. Immunohistochemistry was used to detect the Btk expression in kidney from LN patients and tumor surrounding tissues. Compared with controls, the frequency of Btk+ B cells in SLE patients was upregulated (p < 0.01), and it was significantly correlated with the SLE Disease Activity Index (SLEDAI) (p < 0.01), levels of plasma anti-dsDNA antibody (p < 0.05), the amount of 24-h urine protein (p < 0.05), and levels of plasma C3 (p < 0.05). The frequency of Btk+ B cells in the patients with LN was significantly higher than those without LN (p < 0.05). Although the Btk expression in glomerulus of LN patients was significantly increased compared with controls (p < 0.001), but it had no correlation with the renal pathology activity index, SLEDAI, or 24-h urine protein. In conclusion, the increased expression of Btk in peripheral blood was correlated with LN, indicating that it may be a therapeutic target for SLE.

T follicular helper (Tfh) cells provide help for antigen-specific B cells. We have previously shown that Tfh cell frequency was increased and associated with auto-antibodies in patients with rheumatoid arthritis (RA), suggesting a possible involvement of Tfh cells in its pathogenesis. Mesenchymal stem cells (MSCs) represent a promising alternative cell therapy for RA by modulating T and B cell activation and proliferation. However, it remains unknown whether MSCs have immunoregulation on Tfh cells. In this paper, we have demonstrated that allogeneic MSCs could suppress Tfh cell differentiation in RA patients partly via the production of indoleamine 2,3-dioxygenase (IDO). IFNγ generated from Tfh cell differentiation system induced IDO expression on MSCs. MSCs transplantation (MSCT) into collagen-induced arthritis (CIA) mice prevented arthritis progression by inhibiting both the number and function of Tfh cells in vivo. These findings reveal a novel suppressive function of MSCs in Tfh cells, which has implication in understanding the underlying mechanisms of the immunotherapeutic effects of MSCs on RA patients.

Background Umbilical cord (UC)-derived mesenchymal stem cells (MSCs) have been confirmed to exert therapeutic effects on systemic lupus erythematosus (SLE). Deficiency in SLE macrophages exhibits excessive activation and inefficient clearance of self nuclear antigens. However, whether the benefit effect of UCMSCs on SLE was mediated by regulatory effects on macrophages remains to be elucidated. Objectives We aim to explore whether UCMSCs could educate SLE macrophage to become a kind of alternatively activated macrophage and increase its phagocytic activity. Methods UCMSCs were injected into B6.MRL-Faslpr mice. The therapeutic effects of MSCs transplantation were evaluated by the renal pathology, proteinuria, spleen index, T lymphocyte subpopulation and plasma cells. Murine peritoneal/renal macrophages were isolated to detect the proportion of alternatively activated macrophage (F4/80+CD206+). To determine the phagocytic activity of murine peritoneal/renal macrophages, FITC-labeled flurospheres were added into the cultures. The uptake of FITC-labeled flurospheres was determined by flow cytometry. CD14+ monocytes were isolated from peripheral blood of healthy donors (HC) and SLE patients. We cultured human monocytes for 7 days with macrophage colony-stimulating factor (M-CSF) to generate macrophages, and then cocultured them for 2 more days with UCMSCs in a transwell culture system. The levels of CD206 and phagocytic activity of macrophages were detected by flow cytometry. Results Compared with C57BL/6 mice, B6.MRL-Faslpr mice macrophages exhibited lower level of CD206, the marker of alternatively activated macrophages. In addition, the phagocytic activity of B6.MRL-Faslpr mice macrophages was also decreased. UCMSCs transplantation could rescue both the proportion of CD206+ macrophages and the phagocytic activity. Interestingly, the proportion of CD206+ macrophages was positively correlated with the phagocytic activity. Similar to the lupus mice, macrophages from SLE patients showed lower expression of CD206 and phagocytic activity. SLE macrophages cocultured with UCMSCs consistently increased the expression of CD206 and phagocytic activity. In addition, the up-regulation of phagocytic activity by UCMSCs was only appeared in CD206+ macrophages. This phenomenon was also observed in UCMSCs transplanted SLE patients. Furthermore, the addition of specific neutralizing antibodies/inhibitor/siRNA of HGF, TGFβ1, PGE2 and HO-1 could not reverse the effects of UCMSCs on SLE macrophages. Conclusions UCMSCs could alleviate SLE through promoting the generation of CD206+ macrophage and increasing its phagocytic activity, and these effects was independent of HGF, TGFβ1, PGE2 and HO-1. Disclosure of Interest None declared

Human umbilical cord-derived mesenchymal stem cells (UCMSCs) show therapeutic effects on systemic lupus erythematosus (SLE). Deficiency in functional polarization and phagocytosis in macrophages has been suggested in the pathogenesis of SLE. We found that macrophages from B6.MRL-Faslpr mice exhibited lower level of CD206, the marker for alternatively activated macrophage (AAM, also called M2). In addition, the phagocytic activity of B6.MRL-Faslpr macrophages was also decreased. UCMSC transplantation improved the proportion of CD206+ macrophages and their phagocytic activity in B6.MRL-Faslpr mice. Importantly, macrophages from SLE patients also showed lower expression of CD206 and reduced phagocytic activity, which were corrected by being co-cultured with UCMSCs in vitro and in SLE patients receiving UCMSC transplantation. Mechanistically, we demonstrated that IL-6 was required for the up-regulation of CD206 expression and phagocytic activity of UCMSC-treated SLE macrophages. Our results indicate that UCMSCs alleviate SLE through promoting CD206 expression and phagocytic activity of macrophages in an IL-6 dependent manner.

Background Tremendous progress has been made in the development of non-conventional therapies for rheumatoid arthritis (RA). Mesenchymal stem cells (MSC) present multiple immunosuppressive capacities and may have the potential to exert therapeutic effect in RA. Objectives In this study, the effects of MSC transplantation on established collagen-induced arthritis (CIA) were evaluated and compared with two kinds of biologic agents, anti-tumor necrosis factor (TNF) and anti-CD20 antibody. Methods CIA was induced with the immunization of type II collagen (CII) in DBA/1 mice. Human umbilical cord derived MSC (5×10 6 ), anti-TNF antibody (100μg) and anti-CD20 antibody (200μg) were injected i.p. into mice on day 28 after the immunization, respectively. The control group was treated with PBS or human fibroblasts (5×10 6 ). All mice were sacrificed 3 weeks later and arthritis severity was assessed by clinical and histology scoring. The frequency of CD4 + T cell subsets, B cells and plasma cells in spleen was analyzed by flow cytometry. Serum levels of autoantibody to mouse CII were also determined. The ability of MSC to regulate the balance of T helper cell subsets in CII stimulated CIA CD4 + T cells was assessed in vitro . Results MSC treatment significantly decreased the severity of arthritis and pathology scores, which was comparable to anti-TNF or anti-CD20 treatment. All of the three treatments resulted in a decrease in Th1 subset, but none of them altered the percentage of Th2 subset. Except anti-CD20 treatment, both MSC and anti-TNF treatment significantly decreased Th17 subset. Anti-CD20 treatment depleted nearly half of B220 + cells, and markedly reduced the frequency of plasma cells and serum levels of autoantibody compared to the control group [(738±187) U/ml vs (1817±447) U/ml, P In vitro MSC inhibited the generation of IL17 + or IFNγ + T cells, induced Foxp3 + T cells, and also reduced pathogenic IL17 + IFNγ + or IL-17 + Foxp3 + T cells. Conclusions These results indicated that MSC may have a role in preventing the pathogenic plasticity of CD4 + T cell subsets in arthritic milieu. Umbilical cord (UC)-MSC could exert comparable effects to biologic agents and effectively correct the immune imbalance in CIA. UC-MSC may provide a promising approach for the treatment of RA. Disclosure of Interest None declared

Background: Evidence has accumulated that hypoxia plays a significant role in the pathogenesis and progression of both acute renal injury and chronic renal disease. However, little was known about the effects of hypoxia on lupus nephritis (LN). In the current study, we investigated the expression of hypoxia inducible factor-1 alpha (HIF-1α) in LN. Methods: Renal biopsies from 22 LN patients and 20 patients with renal carcinoma were obtained. In situ HIF-1α expression was examined by immunohistochemical staining, and the relationship between HIF-1α and clinical/pathological features was analyzed. HIF-1α expression in kidney from both MRL/lpr and C57BL/6 mice was detected by immunohistochemical technology. Dimethyloxaloylglycine (DMOG), an inhibitor of HIF-degrading prolylhydroxylases, was utilized to prevent HIF-1α degradation in mouse mesangial cells (MCs). After DMOG treatment, the proliferation and apoptosis rates of mouse MCs were determined. Results: LN patients showed larger amounts of HIF-1α in both glomerular and tubulointerstitial areas. The levels of intraglomerular HIF-1α were closely associated with renal pathology activity index and clinical manifestations in LN patients. In MRL/lpr mice, intraglomerular HIF-1α-positive cells were also significantly increased. Interestingly, the levels of HIF-1α positively correlated with cell density in glomerulus in both LN patients and MRL/lpr mice. Upon treatment with DMOG, the proliferation of MCs was upregulated, and apoptosis was downregulated. Conclusion: HIF-1α is highly expressed in both glomerular and tubulointerstitial tissues in LN, especially in proliferative LN. HIF-1α may promote MCs growth through the induction of proliferation and inhibition of apoptosis, and hence plays an important role in the pathogenesis of LN. © 2014 S. Karger AG, Basel