Integrative Omics Analysis Unravels Microvascular Inflammation-Related Pathways in Kidney Allograft Biopsies Article Swipe
Claire Tinel
,
Baptiste Lamarthée
,
Jasper Callemeyn
,
Elisabet Van Loon
,
Virginia Sauvaget
,
Lise Morin
,
Laïla Aouni
,
Marion Rabant
,
Wilfried Gwinner
,
Pierre Marquet
,
Maarten Naesens
,
Dany Anglicheau
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2021.738795
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2021.738795
In solid-organ transplantation, microRNAs (miRNAs) have emerged as key players in the regulation of allograft cells function in response to injury. To gain insight into the role of miRNAs in antibody-mediated rejection, a rejection phenotype histologically defined by microvascular inflammation, kidney allograft biopsies were subjected to miRNA but also messenger RNA (mRNA) profiling. Using a unique multistep selection process specific to the BIOMARGIN study (discovery cohort, N=86; selection cohort, N=99; validation cohort, N=298), six differentially expressed miRNAs were consistently identified: miR-139-5p (down) and miR-142-3p/150-5p/155-5p/222-3p/223-3p (up). Their expression level gradually correlated with microvascular inflammation intensity. The cell specificity of miRNAs target genes was investigated by integrating their in vivo mRNA targets with single-cell RNA sequencing from an independent allograft biopsy cohort. Endothelial-derived miR-139-5p expression correlated negatively with MHC-related genes expression. Conversely, epithelial-derived miR-222-3p overexpression was strongly associated with degraded renal electrolyte homeostasis and repressed immune-related pathways. In immune cells, miR-150-5p regulated NF-κB activation in T lymphocytes whereas miR-155-5p regulated mRNA splicing in antigen-presenting cells. Altogether, integrated omics enabled us to unravel new pathways involved in microvascular inflammation and suggests that metabolism modifications in tubular epithelial cells occur as a consequence of antibody-mediated rejection, beyond the nearby endothelial compartment.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fimmu.2021.738795
- https://www.frontiersin.org/articles/10.3389/fimmu.2021.738795/pdf
- OA Status
- gold
- Cited By
- 18
- References
- 53
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3209153803
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- OpenAlex ID
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https://openalex.org/W3209153803Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3389/fimmu.2021.738795Digital Object Identifier
- Title
-
Integrative Omics Analysis Unravels Microvascular Inflammation-Related Pathways in Kidney Allograft BiopsiesWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-11-02Full publication date if available
- Authors
-
Claire Tinel, Baptiste Lamarthée, Jasper Callemeyn, Elisabet Van Loon, Virginia Sauvaget, Lise Morin, Laïla Aouni, Marion Rabant, Wilfried Gwinner, Pierre Marquet, Maarten Naesens, Dany AnglicheauList of authors in order
- Landing page
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https://doi.org/10.3389/fimmu.2021.738795Publisher landing page
- PDF URL
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https://www.frontiersin.org/articles/10.3389/fimmu.2021.738795/pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.frontiersin.org/articles/10.3389/fimmu.2021.738795/pdfDirect OA link when available
- Concepts
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microRNA, Inflammation, Biology, Immune system, Transplantation, Immunology, Cancer research, Cell biology, Medicine, Gene, Internal medicine, GeneticsTop concepts (fields/topics) attached by OpenAlex
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18Total citation count in OpenAlex
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2025: 4, 2024: 5, 2023: 2, 2022: 7Per-year citation counts (last 5 years)
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53Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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