Effects of Hypoxia-Inducible Factor-1α Expression and C4d Deposition in Implantation Biopsies on Renal Allograft

Kim, D.J.; Lee, S.; Kim, S.J.; Park, S.G.; Kim, J.S.; Hyun, Seungjoon; Song, Young-Rim; Nam, Eun Sook

doi:10.1016/j.transproceed.2008.07.086

Cited by 2 publications

(2 citation statements)

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“…This family includes the canonical hypoxia‐inducible factor (HIF)‐1α, 16 which facilitates the homing and engraftment of HSCs and progenitor cells and the mobilization of HSCs 18 . The upregulation of HIF‐1α in response to ischaemia may play an essential role in the development of endothelial injury 19 . Dimethyloxallyl glycine (DMOG) is a cell‐permeable and competitive inhibitor of HIF‐PH, which results in HIF‐1α stabilization and accumulation in vitro and in vivo .…”

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confidence: 99%

“…18 The upregulation of HIF-1α in response to ischaemia may play an essential role in the development of endothelial injury. 19 Dimethyloxallyl glycine (DMOG) is a cell-permeable and competitive inhibitor of HIF-PH, which results in HIF-1α stabilization and accumulation in vitro and in vivo. Previous studies have used DMOG to relatively increase the levels of HIF-1α.…”

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Upregulation of HIF‐1α contributes to complement activation in transplantation‐associated thrombotic microangiopathy

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You

et al. 2022

Br J Haematol

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Summary Transplantation‐associated thrombotic microangiopathy (TA‐TMA) is a severe complication of haematopoietic stem cell transplantation (HSCT). Complement activation is involved in the development of TA‐TMA. However, the underlying mechanism is unclear. Therefore, 21 samples of TA‐TMA and 1:1 matched controls were measured for hypoxia‐inducible factor‐1α (HIF‐1α) and complement protein. The mechanism was investigated both in vitro and in vivo. In this study, we found that levels of HIF‐1α were significantly higher in TA‐TMA patients than that in non‐TA‐TMA controls. Upregulation of HIF‐1α induced an increase in membrane‐bound complement C3 and dysfunction of human umbilical vein endothelial cells (HUVECs) in vitro. Increasing HIF‐1α in vivo led to C3 and C5b‐9 deposition in the glomerular endothelial capillary complex, thrombocytopenia, anaemia, and increased serum lactate dehydrogenase (LDH) levels in wild‐type (WT) but not in C3−/− mice subjected to HSCT. High platelet aggregation in peripheral blood and CD41‐positive microthrombi in the kidney were also found in dimethyloxallyl glycine (DMOG)‐treated mice, recapitulating the TA‐TMA phenotype seen in patients. Comprehensive analysis, including DNA array, luciferase reporter assay, chromatin immunoprecipitation (ChIP)‐seq, and quantitative polymerase chain reaction (PCR), revealed that HIF‐1α interacted with the promoter of complement factor H (CFH) to inhibit its transcription. Decreased CFH led to complement activation in endothelial cells.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Upregulation of HIF‐1α contributes to complement activation in transplantation‐associated thrombotic microangiopathy

Pan

You

et al. 2022

Br J Haematol

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Molecular dysfunctions in acute rejection after renal transplantation revealed by integrated analysis of transcription factor, microRNA and long noncoding RNA

et al. 2013

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Acute rejection remains a problem in renal transplantation. To further illustrate the mechanism of rejection, we integrated protein array-based proteomics and RNA microarray-based genomics to investigate the transcription factor, microRNA and long noncoding RNA of biopsies of three patients with acute rejections and a control group. 99 transcription factors were identified in acute rejection biopsies compared to normal renal tissue. We correlated transcription factor data with microRNA and long noncoding RNA data sets and reported the expression of 5 transcription factors (AP-1, AP-4, STATx, c-Myc and p53), 12 miRNAs and 32 lncRNAs in acute rejection biopsies. Pathway analysis demonstrated that over-presentation of transcription factor pathway plays a critical role in acute rejection. This is the first study to comprehensively report the acute rejection transcription factor pathway. Integrative analysis of the transcription factor, microRNA and long noncoding RNA provided an expansive view of molecular signaling pathways in acute rejection after renal transplantation.

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Effects of Hypoxia-Inducible Factor-1α Expression and C4d Deposition in Implantation Biopsies on Renal Allograft

Cited by 2 publications

References 4 publications

Upregulation of HIF‐1α contributes to complement activation in transplantation‐associated thrombotic microangiopathy

Upregulation of HIF‐1α contributes to complement activation in transplantation‐associated thrombotic microangiopathy

Molecular dysfunctions in acute rejection after renal transplantation revealed by integrated analysis of transcription factor, microRNA and long noncoding RNA

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