Expression of hypoxia-inducible factor-1α (HIF-1α) in infiltrating inflammatory cells is associated with chronic allograft dysfunction and predicts long-term graft survival

Yu, Tung Min; Wen, Mei‐Chin; Li, Chi Yuan; Cheng, Chun-Yuan; Wu, Ming; Chen, Cheng Hsu; Shu, Kuo Hsiung

doi:10.1093/ndt/gfs377

Cited by 16 publications

(9 citation statements)

References 43 publications

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“…In addition, HIF‐1α was only expressed in patients with acute rejection . Another study showed that HIF‐1α was upregulated in the area with IF/TA, but this finding was not obtained in protocol biopsies . We chose to use protocol biopsies without acute rejection, and in this setting, HIF‐1α staining was very weak; this is in accordance with the findings of Rosenberger .…”

Section: Discussionsupporting

confidence: 71%

Expression of hypoxia-inducible factor-1α and hepatocyte growth factor in development of fibrosis in the transplanted kidney

et al. 2014

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Summary Late renal graft loss is associated with interstitial fibrosis. Hypoxia‐inducible factor‐1α (HIF‐1α) is thought to facilitate fibrosis through interaction with TGF‐β1, while hepatocyte growth factor (HGF) may act antifibrotic in the kidney allograft. The aim of this study was to investigate the expression of HIF‐1α and HGF in protocol biopsies as possible prognostic biomarkers for renal fibrosis. Thirty‐nine renal transplant recipients were included in the study. Protocol biopsies performed 1 and 2 years after transplantation were used for immunohistochemistry analysis. The correlation between HIF‐1α/HGF and the Banff score was analysed. In addition, progression in renal fibrosis and graft survival among recipients with high or low expression of HIF‐1α/HGF after transplantation was compared. There was no significant correlation between fibrosis and the HIF‐1α expression 1 and 2 years after transplantation, but an inverse significant correlation between the HGF expression and the fibrosis score 1 year after transplantation was shown. Even when adjusting for human leucocyte antigen mismatches, there was a significant relationship between fibrosis and HGF expression. Graft survival was not significantly correlated to HIF‐1α or HGF at 1 year, although the trend was towards better graft survival with high HGF. HGF may have antifibrotic effects in human renal transplants. (Central.Denmark.Region.Committee number: 1‐10‐72‐318‐13)

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Section: Discussionsupporting

confidence: 71%

Expression of hypoxia-inducible factor-1α and hepatocyte growth factor in development of fibrosis in the transplanted kidney

et al. 2014

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“…HIF-1αparticipates in fibrosis through regulating the expression of connective tissue growth factor (CTGF). Moreover, Yu et al evaluated renal transplant recipients who underwent renal allograft biopsy with IF/TA, and found the expression of HIF-1α protein in filtrating inflammatory cells in areas with IF/TA in patients with chronic allograft dysfunction [ 62 ]. The expression of HIF-1α in the infiltrating macrophages/monocytes in chronic allograft dysfunction provides a novel role of HIF-1α in inflammation that may be caused by hypoxia which is not alloreactive [ 63 ].…”

Section: Reviewmentioning

confidence: 99%

Recent advances in renal interstitial fibrosis and tubular atrophy after kidney transplantation

Zhuang

2014

Fibrogenesis Tissue Repair

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Although kidney transplantation has been an important means for the treatment of patients with end stage of renal disease, the long-term survival rate of the renal allograft remains a challenge. The cause of late renal allograft loss, once known as chronic allograft nephropathy, has been renamed “interstitial fibrosis and tubular atrophy” (IF/TA) to reflect the histologic pattern seen on biopsy. The mechanisms leading to IF/TA in the transplanted kidney include inflammation, activation of renal fibroblasts, and deposition of extracellular matrix proteins. Identifying the mediators and factors that trigger IF/TA may be useful in early diagnosis and development of novel therapeutic strategies for improving long-term renal allograft survival and patient outcomes. In this review, we highlight the recent advances in our understanding of IF/TA from three aspects: pathogenesis, diagnosis, and treatment.

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“…Some studies claim that hypoxia recruits inflammatory cells of innate and adaptive immunity and exacerbates the inflammatory process; this sensitive response is mediated by HIF‐1α that operates a complex inflammatory response in microenvironments, playing an important role in renal pathogenesis. Yu et al recruited 32 patients with a diagnosis of postgraft CKD, with microcirculation impairment among inflammatory renal cell infiltrates. They found an increase in HIF‐1α expression, chronic interstitial modification, and low haemoglobin level, unlike patients with stable renal transplants who exhibit low HIF‐1α expression.…”

Section: Discussionmentioning

confidence: 99%

Role of hypoxia‐inducible factor 1α as a potential biomarker for renal diseases—A systematic review

Encinas

Foncesca

Perez

et al. 2019

Cell Biochemistry & Function

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Renal cells need oxygen for homeostasis; it is known for adjusting cellular functioning and the energy obtainment have a broad relationship with cellular respiration, through the O2 bioavailability. O2 homeostasis regulation in the kidney is mediated by hypoxia‐inducible factors (HIFs). HIF is divided into three α isoforms, represented by HIF‐1α, HIF‐2α, and HIF‐3α in addition to three paralogs of HIF‐1β; these are involved in some metabolic processes, as well as in the pathogenesis of several diseases. Renal biopsy analyses of patients and experimental animal models aim to understand the relationship between HIF and protection against developing renal diseases or the induction of their onset, being thus this molecule can be considered a potential biomarker of renal disease. We carried out a systematic review to which we included studies on HIF‐1α and renal disease in the last 5 years (2013‐2018) in researches with humans and/or animal model through searches in three databases: LILACS, PubMed, and SciELO by two researchers. We obtained 22 articles that discussed the relationship with HIF as inductor or protector against renal disease and no relation between HIF and renal. We observed controversies remain regarding the relation between of HIF with renal diseases; this may be related to the different intracellular pathways mediated by HIF‐1α, thereby determining differentiated cellular responses.

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Expression of hypoxia-inducible factor-1α (HIF-1α) in infiltrating inflammatory cells is associated with chronic allograft dysfunction and predicts long-term graft survival

Abstract: We first demonstrated the expression of HIF-1α protein among infiltrating inflammatory cells in areas with IF/TA in patients with chronic allograft dysfunction.

Cited by 16 publications

References 43 publications

Expression of hypoxia-inducible factor-1α and hepatocyte growth factor in development of fibrosis in the transplanted kidney

Expression of hypoxia-inducible factor-1α and hepatocyte growth factor in development of fibrosis in the transplanted kidney

Recent advances in renal interstitial fibrosis and tubular atrophy after kidney transplantation

Role of hypoxia‐inducible factor 1α as a potential biomarker for renal diseases—A systematic review

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