Differential expression of genes related to calcineurin and mTOR signaling and regulatory miRNAs in peripheral blood from kidney recipients under tacrolimus-based therapy

Bonezi, Vivian; Genvigir, Fabiana Dalla Vecchia; Salgado, Patrícia de Cássia; Felipe, Cláudia Rosso; Tedesco‐Silva, Hélio; Medina‐Pestana, José Osmar; Cerda, Álvaro; Doi, Sonia Q.; Hirata, Mário Hiroyuki; Hirata, Rosário Dominguez Crespo

doi:10.21037/atm-20-1757

Cited by 4 publications

(3 citation statements)

References 51 publications

(53 reference statements)

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“…2F and 4E ). MAP kinase and NF-κB activity are involved in corticosteroid signaling pathways in transplant immunosuppression ( 81 ) and immune suppression–induced nephrotoxicity ( 82 , 83 ), giving further credence to investigation of the scaffold implant as a means to monitor common immunosuppression regimes consisting of calcineurin inhibitors and corticosteroids. Secreted fibrinogen-like protein 2 (FGL2) by CD4 T cells potentially mediates acute graft rejection and is induced by tumor necrosis factor–α or interferon-γ stimulation through MAP kinase signaling ( 84 ).…”

Section: Discussionmentioning

confidence: 99%

Biomarkers from subcutaneous engineered tissues predict acute rejection of organ allografts

Urie,

Morris,

Farris

et al. 2024

Sci. Adv.

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Invasive graft biopsies assess the efficacy of immunosuppression through lagging indicators of transplant rejection. We report on a microporous scaffold implant as a minimally invasive immunological niche to assay rejection before graft injury. Adoptive transfer of T cells into Rag2 −/− mice with mismatched allografts induced acute cellular allograft rejection (ACAR), with subsequent validation in wild-type animals. Following murine heart or skin transplantation, scaffold implants accumulate predominantly innate immune cells. The scaffold enables frequent biopsy, and gene expression analyses identified biomarkers of ACAR before clinical signs of graft injury. This gene signature distinguishes ACAR and immunodeficient respiratory infection before injury onset, indicating the specificity of the biomarkers to differentiate ACAR from other inflammatory insult. Overall, this implantable scaffold enables remote evaluation of the early risk of rejection, which could potentially be used to reduce the frequency of routine graft biopsy, reduce toxicities by personalizing immunosuppression, and prolong transplant life.

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Section: Discussionmentioning

confidence: 99%

Biomarkers from subcutaneous engineered tissues predict acute rejection of organ allografts

Urie,

Morris,

Farris

et al. 2024

Sci. Adv.

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“…This is expected in these patients who are maintained on multiple therapies for immunosuppression. The immune pathways identified are relevant in transplantation (Fric et al 2014; Wang et al 2015; Bonezi et al 2020). Indeed, several genes of the calcineurin pathways were down regulated in these patients who are maintained on calcineurin inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Cell-free Chromatin Immunoprecipitation to detect molecular pathways in Physiological and Disease States

Jang

Markowitz

Andagie

et al. 2023

Preprint

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Patient monitoring is a cornerstone in clinical practice to define disease phenotypes and guide clinical management. Unfortunately, this is often reliant on invasive and/or less sensitive methods that do not provide deep phenotype assessments of disease state to guide treatment. This paper examined plasma cell-free DNA chromatin immunoprecipitation sequencing (cfChIP-seq) to define molecular gene sets in physiological and heart transplant patients taking immunosuppression medications. We show cfChIP-seq reliably detect gene signals that correlate with gene expression. In healthy controls and in heart transplant patients, cfChIP-seq reliably detected housekeeping genes. cfChIP-seq identified differential gene signals of the relevant immune and non-immune molecular pathways that were predominantly downregulated in immunosuppressed heart transplant patients compared to healthy controls. cfChIP-seq also identified tissue sources of cfDNA, detecting greater cell-free DNA from cardiac, hematopoietic, and other non-hematopoietic tissues such as the pulmonary, digestive, and neurological tissues in transplant patients than healthy controls. cfChIP-seq gene signals were reproducible between patient populations and blood collection methods. cfChIP-seq may therefore be a reliable approach to provide dynamic assessments of molecular pathways and tissue injury associated to disease.

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“…As a proxy for gene expression, cfChIP-seq reliably detected housekeeping genes in healthy control subjects and heart transplant recipients, and differential immune pathways ( Fric et al, 2014 ; Wang et al, 2015 ; Bonezi et al, 2020 ) relevant in transplantation. Indeed, several genes of the calcineurin or mTOR pathways were down-regulated in these patients who are maintained on calcineurin and mTOR inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Cell-free chromatin immunoprecipitation to detect molecular pathways in heart transplantation

Jang,

Markowitz,

Andargie

et al. 2023

Life Sci. Alliance

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Existing monitoring approaches in heart transplantation lack the sensitivity to provide deep molecular assessments to guide management, or require endomyocardial biopsy, an invasive and blind procedure that lacks the precision to reliably obtain biopsy samples from diseased sites. This study examined plasma cell-free DNA chromatin immunoprecipitation sequencing (cfChIP-seq) as a noninvasive proxy to define molecular gene sets and sources of tissue injury in heart transplant patients. In healthy controls and in heart transplant patients, cfChIP-seq reliably detected housekeeping genes. cfChIP-seq identified differential gene signals of relevant immune and nonimmune molecular pathways that were predominantly down-regulated in immunosuppressed heart transplant patients compared with healthy controls. cfChIP-seq also identified cell-free DNA tissue sources. Compared with healthy controls, heart transplant patients demonstrated greater cell-free DNA from tissue types associated with heart transplant complications, including the heart, hematopoietic cells, lungs, liver, and vascular endothelium. cfChIP-seq may therefore be a reliable approach to profile dynamic assessments of molecular pathways and sources of tissue injury in heart transplant patients.

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Differential expression of genes related to calcineurin and mTOR signaling and regulatory miRNAs in peripheral blood from kidney recipients under tacrolimus-based therapy

Cited by 4 publications

References 51 publications

Biomarkers from subcutaneous engineered tissues predict acute rejection of organ allografts

Biomarkers from subcutaneous engineered tissues predict acute rejection of organ allografts

Cell-free Chromatin Immunoprecipitation to detect molecular pathways in Physiological and Disease States

Cell-free chromatin immunoprecipitation to detect molecular pathways in heart transplantation

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