Hypoxia-inducible Factor-1α directs renal regeneration induced by decellularized scaffolds

Yu, Yan; Cui, Hao; Chen, Chuan; Wen, Gen; Xu, Jia; Zheng-Lin, Binbin; Zhang, Jianse; Wang, Chunyang; Chai, Yimin; Mei, Jin

doi:10.1016/j.biomaterials.2018.02.045

Cited by 26 publications

(22 citation statements)

References 47 publications

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“…The expression of HIF-1 α and catalase in S-shaped bodies was downregulated instantly following hyperoxia on the 1st postnatal day. Since the expression of HIF-1 α and catalase is vital in nephrogenesis [62, 63], our findings above indicate that the nephrogenic role of HIF-1 α and catalase expression is attenuated early by hyperoxia exposure during the S-shaped body stage. The long-term effect of hyperoxia on the expression of HIF-1 α and catalase in the proximal tubules was also investigated in the current study, which demonstrated that HIF-1 α and catalase expression in mature proximal tubules was downregulated following neonatal hyperoxia.…”

Section: Discussionmentioning

confidence: 69%

Proximal Tubular Development Is Impaired with Downregulation of MAPK/ERK Signaling, HIF-1α, and Catalase by Hyperoxia Exposure in Neonatal Rats

You

2019

Oxidative Medicine and Cellular Longevity

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Supplemental oxygen therapy (hyperoxia) is a widely used treatment for alveolar hypoxia in preterm infants. Despite being closely monitored, hyperoxia exposure is believed to undermine neonatal nephrogenesis and renal function caused by elevated oxidative stress. Previous studies have mostly focused on the hyperoxia-induced impairment of glomerular development, while the long-term impact of neonatal hyperoxia on tubular development and the regulatory component involved in this process remain to be clarified. Here, we examined tubular histology and apoptosis, along with the expression profile of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling, hypoxia-inducible factor 1α (HIF-1α), and catalase, following hyperoxia exposure in neonatal rats. Hematoxylin and eosin (H&E) staining revealed the early disappearance of the nephrogenic zone, as well as dilated lumens and reduced epithelial cells, of mature proximal tubules following neonatal hyperoxia. A robust increase in tubular cell apoptosis caused by neonatal hyperoxia was found using a TUNEL assay. Moreover, neonatal hyperoxia altered renal MAPK/ERK signaling activity and downregulated the expression of HIF-1α and catalase in the proximal tubules throughout nephrogenesis from S-shaped bodies to mature proximal tubules. Cell apoptosis in the proximal tubules was positively correlated with HIF-1α expression on the 14th postnatal day. Our data indicates that proximal tubular development is impaired by neonatal hyperoxia, which is accompanied by altered MAPK/ERK signaling as well as downregulated HIF-1α and catalase. Therapeutic management that targets MAPK/ERK signaling, HIF-1α, or catalase may serve as a protective agent against hyperoxia-induced oxidative damage to neonatal proximal tubules.

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Section: Discussionmentioning

confidence: 69%

Proximal Tubular Development Is Impaired with Downregulation of MAPK/ERK Signaling, HIF-1α, and Catalase by Hyperoxia Exposure in Neonatal Rats

You

2019

Oxidative Medicine and Cellular Longevity

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“…DMOG is a cell permeable competitive inhibitor of prolyl hydroxylase domain-containing proteins such as the PHDs. DMOG has been shown to activate HIF1α, under normoxic (21% O 2 ) conditions in a wide variety of cell types [93,94] including lens cells [23]. Cleavage Under Targets & Release Using Nuclease (CUT&RUN) [24,25] was performed on un xed permeabilized primary lens cells incubated with a HIF1α-speci c ChIP grade antibody (Abcam, ab2185) and an IgG negative control antibody (Invitrogen, prod no: 10500c) to elucidate genome-wide HIF1α-DNA binding complexes.…”

Section: Cutandrun On Dmog-treated Lens Cells and Bioinformatics Analysismentioning

confidence: 99%

A Functional Map of Genomic HIF1α-DNA Complexes in The Eye Lens Revealed Through Multiomics Analysis

Disatham

Brennan

Chauss

et al. 2021

Preprint

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Background: During eye lens development the fetal vasculature regresses leaving the lens without a direct oxygen source. Both embryonically and throughout adult life, the lens contains a decreasing oxygen gradient from the surface to the core that parallels the natural differentiation of immature surface epithelial cells into mature core transparent fiber cells. These properties of the lens suggest a potential role for hypoxia in the regulation of genes required for mature lens structure and function. Since HIF1α is a master regulator of the hypoxic response, these lens properties also implicate HIF1α as a potential requirement for lens formation and homeostasis. Here, we employed a multiomics approach combining CUT&RUN, RNAseq and ATACseq analysis to establish the genomic complement of lens HIF1α binding sites, genes activated or repressed by HIF1α and the chromatin states of HIF1α-regulated genes.Results: CUT&RUN analysis revealed 8,375 HIF1α-DNA binding complexes in the chick lens genome. 1,190 HIF1α-DNA binding complexes were significantly clustered within chromatin accessible regions (χ2 test p < 1x10-55) identified by ATACseq. Formation of the identified HIF1α-DNA complexes paralleled the activation or repression of 526 genes, 116 of which contained HIF1α binding sites within 10kB of the transcription start sites. Some of the identified HIF1α genes have previously established lens functions while others have novel functions never before examined in the lens. GO and pathway analysis of these genes implicate HIF1α in the control of a wide-variety of cellular pathways potentially critical for lens formation, structure and function including glycolysis, cell cycle regulation, chromatin remodeling, Notch and Wnt signaling, differentiation, development, and transparency. Conclusions: These data establish the first functional map of genomic HIF1α-DNA complexes in the eye lens. They identify HIF1α as an important regulator of a wide-variety of genes previously shown to be critical for lens formation and function and they reveal a requirement for HIF1α in the regulation of a wide-variety of genes not yet examined for lens function. They support a requirement for HIF1α in lens development, structure and function and they provide a basis for understanding the potential roles and requirements for HIF1α in the development, structure and function of more complex tissues.

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“…The use of scaffolds has contributed to tissue reconstruction and regeneration. [13,14] However, up to date, accepted standardized thyroid decellularization protocol is lacking.…”

Section: Introductionmentioning

confidence: 99%

Rabbit thyroid extracellular matrix as a 3D bioscaffold for thyroid bioengineering: a preliminary in vitro study

Weng

Xie

et al. 2021

Preprint

Self Cite

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Background: Advances in regenerative medicine technologies have been strongly proposed in the management of thyroid diseases. Mechanistically, the adoption of thyroid bioengineering requires a scaffold that shares a similar three dimensional (3D) space structure, biomechanical properties, protein component, and cytokines to the native extracellular matrix (ECM).Methods: 24 male New Zealand white rabbits were used in this experimental study. The rabbit thyroid glands were decellularized by immersion/agitation decellularization protocol. The 3D thyroid decellularization scaffolds were tested with histological and immunostaining analyses, scanning electron microscopy, DNA quantification, mechanical properties test, cytokine assay and cytotoxicity assays. Meanwhile, the decellularization scaffold were seeded with human thyroid follicular cells, cell proliferation and thyroid peroxidase were determined to explore the biocompatibility in vitro.Results: Notably, through the imaging studies, it was distinctly evident that our protocol intervention minimized cellular materials and maintained the 3D spatial structure, biomechanical properties, ECM composition, and biologic cytokine. Consequently, the decellularization scaffold was seeded with human thyroid follicular cells, thus strongly revealing its potential in reinforcing cell adhesion, proliferation, and preserve important protein expression.Conclusions: The adoption of our protocol to generate a decellularized thyroid scaffold can potentially be utilized in transplantation to manage thyroid diseases through thyroid bioengineering.

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Hypoxia-inducible Factor-1α directs renal regeneration induced by decellularized scaffolds

Cited by 26 publications

References 47 publications

Proximal Tubular Development Is Impaired with Downregulation of MAPK/ERK Signaling, HIF-1α, and Catalase by Hyperoxia Exposure in Neonatal Rats

Proximal Tubular Development Is Impaired with Downregulation of MAPK/ERK Signaling, HIF-1α, and Catalase by Hyperoxia Exposure in Neonatal Rats

A Functional Map of Genomic HIF1α-DNA Complexes in The Eye Lens Revealed Through Multiomics Analysis

Rabbit thyroid extracellular matrix as a 3D bioscaffold for thyroid bioengineering: a preliminary in vitro study

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Hypoxia-inducible Factor-1α directs renal regeneration induced by decellularized scaffolds

Cited by 26 publications

References 47 publications

Proximal Tubular Development Is Impaired with Downregulation of MAPK/ERK Signaling, HIF-1α, and Catalase by Hyperoxia Exposure in Neonatal Rats

Proximal Tubular Development Is Impaired with Downregulation of MAPK/ERK Signaling, HIF-1α, and Catalase by Hyperoxia Exposure in Neonatal Rats

A Functional Map of Genomic HIF1α-DNA Complexes in The Eye Lens Revealed Through Multiomics Analysis

Rabbit thyroid extracellular matrix as a 3D bioscaffold for thyroid bioengineering: a&nbsp;preliminary&nbsp;in&nbsp;vitro&nbsp;study

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Rabbit thyroid extracellular matrix as a 3D bioscaffold for thyroid bioengineering: a preliminary in vitro study