Major histocompatibility complexes are up‐regulated in glomerular endothelial cells via activation of c‐Jun N‐terminal kinase in 5/6 nephrectomy mice

Zhu, Dong; Tang, Qin; Yu, Baixue; Mao, Meng; Liu, Wenjie; Li, Jiawei; Zhu, Tongyu; Vanhoutte, Paul M.; Leung, Susan W.S.; Zhang, Yi; Shi, Yi

doi:10.1111/bph.15237

Cited by 10 publications

(9 citation statements)

References 64 publications

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“…In addition, the previously reported haematopoiesis- and immunomodulation-related genes [ 51 – 56 ] in BM EPCs were detected by RNA-seq (Fig. 2 H) and verified by qRT-PCR.…”

Section: Resultssupporting

confidence: 75%

Dysfunctional bone marrow endothelial progenitor cells are involved in patients with myelodysplastic syndromes

et al. 2022

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Background Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal disorders characterized by ineffective haematopoiesis and immune deregulation. Emerging evidence has shown the effect of bone marrow (BM) endothelial progenitor cells (EPCs) in regulating haematopoiesis and immune balance. However, the number and functions of BM EPCs in patients with different stages of MDS remain largely unknown. Methods Patients with MDS (N = 30), de novo acute myeloid leukaemia (AML) (N = 15), and healthy donors (HDs) (N = 15) were enrolled. MDS patients were divided into lower-risk MDS (N = 15) and higher-risk MDS (N = 15) groups according to the dichotomization of the Revised International Prognostic Scoring System. Flow cytometry was performed to analyse the number of BM EPCs. Tube formation and migration assays were performed to evaluate the functions of BM EPCs. In order to assess the gene expression profiles of BM EPCs, RNA sequencing (RNA-seq) were performed. BM EPC supporting abilities of haematopoietic stem cells (HSCs), leukaemia cells and T cells were assessed by in vitro coculture experiments. Results Increased but dysfunctional BM EPCs were found in MDS patients compared with HDs, especially in patients with higher-risk MDS. RNA-seq indicated the progressive change and differences of haematopoiesis- and immune-related pathways and genes in MDS BM EPCs. In vitro coculture experiments verified that BM EPCs from HDs, lower-risk MDS, and higher-risk MDS to AML exhibited a progressively decreased ability to support HSCs, manifested as elevated apoptosis rates and intracellular reactive oxygen species (ROS) levels and decreased colony-forming unit plating efficiencies of HSCs. Moreover, BM EPCs from higher-risk MDS patients demonstrated an increased ability to support leukaemia cells, characterized by increased proliferation, leukaemia colony-forming unit plating efficiencies, decreased apoptosis rates and apoptosis-related genes. Furthermore, BM EPCs induced T cell differentiation towards more immune-tolerant cells in higher-risk MDS patients in vitro. In addition, the levels of intracellular ROS and the apoptosis ratios were increased in BM EPCs from MDS patients, especially in higher-risk MDS patients, which may be therapeutic candidates for MDS patients. Conclusion Our results suggest that dysfunctional BM EPCs are involved in MDS patients, which indicates that improving haematopoiesis supporting ability and immuneregulation ability of BM EPCs may represent a promising therapeutic approach for MDS patients.

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“…In addition, the previously reported haematopoiesis- and immunomodulation-related genes [ 51 – 56 ] in BM EPCs were detected by RNA-seq (Fig. 2 H) and verified by qRT-PCR.…”

Section: Resultssupporting

confidence: 75%

Dysfunctional bone marrow endothelial progenitor cells are involved in patients with myelodysplastic syndromes

et al. 2022

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“…9 There are variations of the 5/6 nephrectomy procedure, ranging from differences in the incision locations, differences in the kidney that experienced unilateral nephrectomy (right or left kidney), differences in the duration of the first and second surgery (when using 2 stages of surgery), and differences in the length of observation before the animal was terminated (Table 1). Incisions can be in the form of a laparotomy, 11,12 dorsal, 13,14 and an incision in the flank region. 6,9,10,[15][16][17] The majority of surgical procedures are carried out in 2 steps, although there are studies that are carried out in 1 step.…”

Section: Resultsmentioning

confidence: 99%

Subtotal Nephrectomy as a Model of Chronic Kidney Disease: A Systematic Review

Putu Nita Cahyawati,

Bagus Komang Satriyasa

2021

IJPHRD

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Background: Subtotal nephrectomy (5/6 nephrectomy) is one of the most widely used animal models for modifying chronic kidney disease. Animal models of kidney disease play an important role to understand pathophysiology, progressivity, and therapies for the disease. The development of animal models that mimic the conditions in human disease is still a challenge. Methods:We conducted a systematic search in the main biomedical databases MEDLINE (PubMed) and the Directory of Open Access Journals (DOAJ) Conclusion:The subtotal nephrectomy procedure is a good model for chronic kidney disease. The kidney damage on this model most closely mimics with kidney damage in humans. This procedure used to remove or destroys 5/6 parts of the kidney, leaving only 1/3 of the kidney mass. There are variations to this procedure. Variations included in the type of incision, the location of the uninephrectomy, the type of ligase/ablation, the operation stage (one or two steps), the length of time between 2 operating procedures, the length of time for observation, and the type of animal used. Variations procedure in subtotal nephrectomy model have different effects on biochemical parameters, morphology, and markers of kidney damage.

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“…Renal cortex of control mice, 6-wk-old db/db mice (high serum glucose levels without organ damage), and 10-wk-old db/db mice [shown diabetic complications, including cognitive dysfunction ( 20 ) and albuminuria] were collected and digested in Hanks buffer with 10 mg/mL of collagenase IV (Sigma-Aldrich) and 200 U/mL of DNase I (Invitrogen, Carlsbad, MO) at 37°C for 20 min. Renal cortex samples were dissociated using a gentle MACS Dissociation (Miltenyi Biotec, Bergisch Gladbach, Germany) according to the manufacturer’s instructions ( 21 ).…”

Section: Methodsmentioning

confidence: 99%

“…After perfusion of ice-cold PBS with 8 × 10 7 Dynabead ferric beans M450 (Invitrogen, Carlsbad, MO) for 20 min (2 mL/min), mouse kidneys were digested with collagenase A (Roche, Basel, Switzerland) at 37°C for 30 min and filtered with 100-µm cell strainers. The glomeruli, collected by a magnetic particle concentrator (Invitrogen, Carlsbad, MO), were further incubated with Hanks buffer with 10 mg/mL of collagenase IV (Sigma-Aldrich) and 200 U/mL of DNase I (Invitrogen, Carlsbad, MO) at 37°C for 20 min ( 21 ). Glomerular cells, stained for lineage markers CD31 (endothelial cells, 1:100, 551262, RRID:AB_398497, BD PharMingen), Podoplanin (podocytes, 1:100, 566390, RRID:AB_2739721, BD PharMingen), and CD90 (mesangial cells, 1:100, 561973, RRID:AB_10898011, BD PharMingen) were sorted using a BD AriaIII (BD Bioscience, Switzerland).…”

Section: Methodsmentioning

confidence: 99%

Glycolytic enzyme PFKFB3 regulates sphingosine 1-phosphate receptor 1 in proangiogenic glomerular endothelial cells under diabetic condition

Yu,

Shen,

et al. 2023

American Journal of Physiology-Cell Physiology

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Glomerular angiogenesis is a characteristic feature of diabetic nephropathy (DN). Enhanced glycolysis plays a crucial role in angiogenesis. The present study was designed to investigate the role of glycolysis in glomerular endothelial cells (GECs) in a mouse model of DN. Mouse renal cortex and isolated glomerular cells were collected for single-cell and RNA sequencing. Cultured GECs were exposed to high glucose in the presence (proangiogenic) and absence of a vascular sprouting regimen. MicroRNA-590-3p was delivered by lipofectamine in vivo and in vitro. In the present study, a subgroup of GECs with proangiogenic features was identified in diabetic kidneys by using sequencing analyses. In cultured proangiogenic GECs, high glucose increased glycolysis and PFKFB3 protein expression, which were inhibited by overexpressing miRNA-590-3p. Mimics of miRNA-590-3p also increased S1pR1 expression, an angiogenesis regulator, in proangiogenic GECs challenged with high glucose. Inhibition of PFKFB3 by pharmacological and genetic approaches upregulated S1pR1 protein in vitro. Mimics of miRNA-590-3p significantly reduced migration and angiogenic potential in proangiogenic GECs challenged with high glucose. Ten-week-old type 2 diabetic mice had elevated urinary albumin levels, reduced renal cortex miRNA-590-3p expression, and disarrangement of glomerular endothelial cell fenestration. Overexpressing miRNA-590-3p via perirenal adipose tissue injection restored endothelial cell fenestration and reduced urinary albumin levels in diabetic mice. Therefore, the present study identifies a subgroup of GECs with proangiogenic features in mice with DN. Local administration of miRNA-590-3p mimics reduces glycolytic rate and upregulates S1pR1 protein expression in proangiogenic GECs. The protective effects of miRNA-590-3p provide therapeutic potential in DN treatment.

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Major histocompatibility complexes are up‐regulated in glomerular endothelial cells via activation of c‐Jun N‐terminal kinase in 5/6 nephrectomy mice

Cited by 10 publications

References 64 publications

Dysfunctional bone marrow endothelial progenitor cells are involved in patients with myelodysplastic syndromes

Dysfunctional bone marrow endothelial progenitor cells are involved in patients with myelodysplastic syndromes

Subtotal Nephrectomy as a Model of Chronic Kidney Disease: A Systematic Review

Glycolytic enzyme PFKFB3 regulates sphingosine 1-phosphate receptor 1 in proangiogenic glomerular endothelial cells under diabetic condition

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