Expression of Mitochondrial-Encoded Genes in Blood Differentiate Acute Renal Allograft Rejection

Roedder, Silke; Sigdel, Tara K.; Hsieh, Szu‐Chuan; Cheeseman, Jennifer A.; Metes, Diana; Macedo, Camila; Reed, Elaine F.; Gritsch, H. Albin; Zeevi, Adriana; Shapiro, Ron; Kirk, Allan D.; Sarwal, Minnie M.

doi:10.3389/fmed.2017.00185

Cited by 8 publications

(6 citation statements)

References 26 publications

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“…When the kidney is damaged, plasma dmtDNA levels increase, which may be accompanied by more antigen exposure, resulting in increased AR incidence. In contrast, increased dmtDNA levels may not only trigger inflammation, but may also lead to AR [ 28 , 29 ]. Elevated dmtDNA levels are an independent risk factor not only for DGF, but also for AR.…”

Section: Discussionmentioning

confidence: 99%

Donor plasma mitochondrial DNA is associated with antibody-mediated rejection in renal allograft recipients

Han

Sun

Huang

et al. 2021

Aging

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We previously showed that donor plasma mitochondrial DNA (dmtDNA) levels were correlated with renal allograft function. The aim of the current study was to determine whether dmtDNA levels are associated with the occurrence of antibody-mediated rejection (ABMR). This is a retrospective open cohort study comprised of 167 donors and 323 recipients enrolled from January 2015 to December 2017. We quantified the mtDNA level present in donor plasma using quantitative real-time polymerase chain reaction. The average plasma dmtDNA level in the acute rejection (AR) group was higher than that of the control group (0.156 versus 0.075, p<0.001). Multivariate logistic regression analysis showed that dmtDNA levels were also significantly associated with AR (OR=1.588, 95% CI 1.337-4.561, p<0.001). When the dmtDNA level was >0.156, the probability of AR was 62.9%. The plasma dmtDNA level in the ABMR group was significantly higher than that of the T cell-mediated rejection group (0.185 versus 0.099, p=0.032). The area under the receiver operating characteristic curve of dmtDNA for prediction of ABMR was as high as 0.910 (95% CI 0.843-0.977). We demonstrated that plasma dmtDNA was an independent risk factor for ABMR, which is valuable in organ evaluation. dmtDNA level is a possible first predictive marker for ABMR.

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Section: Discussionmentioning

confidence: 99%

Donor plasma mitochondrial DNA is associated with antibody-mediated rejection in renal allograft recipients

Han

Sun

Huang

et al. 2021

Aging

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“…Nonsteroidal anti‐inflammatory drugs (NSAIDs) are widely used to alleviate inflammation (Moore et al., 2019 ). Even prolonged use of NSAIDs can result in gastric and renal toxicity (Magni et al., 2021 ), mainly due to the nonselective inhibition of COX‐1 and COX‐2 (Roedder et al., 2017 ). It is believed that currently used anti‐inflammatory drugs, including opiates and non‐NSAIDs, have associated toxic effects like gastric and renal ulcers and low potentiality (Coban & Degim, 2020 ; Phueanpinit et al., 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Hypoglycemic, anti‐inflammatory, and neuroprotective potentials of crude methanolic extract from Acacia nilotica L. – results of an in vitro study

Rauf,

Ibrahim,

Alomar

et al. 2024

Food Science & Nutrition

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Acacia nilotica L., also known as babul, belonging to the Fabaceae family and the Acacia genus, is typically used for ornamental purposes and also as a medicinal plant found in tropical and subtropical areas. This plant is a rich source of bioactive compounds. The current study aimed to elucidate the hypoglycemic, anti‐inflammatory, and neuroprotective potential of A. nilotica's crude methanolic extract. The results of the in vitro antidiabetic assay revealed that methanolic extract of A. nilotica inhibited the enzyme α‐glucosidase (IC50: 33 μg mL−1) and α‐amylase (IC50: 17 μg mL−1) in a dose‐dependent manner. While in the anticholinesterase enzyme inhibitory assay, maximum inhibition was shown by the extract against acetylcholinesterase (AChE) (637.01 μg mL−1) and butyrylcholinesterase (BChE) (491.98 μg mL−1), with the highest percent inhibition of 67.54% and 71.50% at 1000 μg mL−1, respectively. This inhibitory potential was lower as compared to the standard drug Galantamine that exhibited 82.43 and 89.50% inhibition at the same concentration, respectively. Moreover, the methanolic extract of A. nilotica also significantly inhibited the activities of cyclooxygenase 2 (COX‐2) and 5‐lipoxygenase (5‐LOX) in a concentration‐dependent manner. The percent inhibitory activity of 5‐LOX and COX‐2 ranged from 42.47% to 71.53% and 43.48% to 75.22%, respectively. Furthermore, in silico, in vivo, and clinical investigations must be planned to validate the above‐stated bioactivities of A. nilotica.

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“…Several studies have shown an important link between mitochondrial dysregulation and allograft rejection 19–26 . Mitochondrial fusion/fission plays an important role in regulating mitochondrial fitness and cellular health.…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have shown an important link between mitochondrial dysregulation and allograft rejection. [19][20][21][22][23][24][25][26] Mitochondrial fusion/fission plays an important role in regulating mitochondrial fitness and cellular health. Fusion is mediated by several key machinery proteins, including mitofusin-1, mitofusin-2, and optic atrophy-1.…”

Section: Introductionmentioning

confidence: 99%

Modulating donor mitochondrial fusion/fission delivers immunoprotective effects in cardiac transplantation

Tran

Alawieh

et al. 2022

American Journal of Transplantation

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Early insults associated with cardiac transplantation increase the immunogenicity of donor microvascular endothelial cells (ECs), which interact with recipient alloreactive memory T cells and promote responses leading to allograft rejection. Thus, modulating EC immunogenicity could potentially alter T cell responses. Recent studies have shown modulating mitochondrial fusion/fission alters immune cell phenotype. Here, we assess whether modulating mitochondrial fusion/fission reduces EC immunogenicity and alters EC‐T cell interactions. By knocking down DRP1, a mitochondrial fission protein, or by using the small molecules M1, a fusion promoter, and Mdivi1, a fission inhibitor, we demonstrate that promoting mitochondrial fusion reduced EC immunogenicity to allogeneic CD8+ T cells, shown by decreased T cell cytotoxic proteins, decreased EC VCAM‐1, MHC‐I expression, and increased PD‐L1 expression. Co‐cultured T cells also displayed decreased memory frequencies and Ki‐67 proliferative index. For in vivo significance, we used a novel murine brain‐dead donor transplant model. Balb/c hearts pretreated with M1/Mdivi1 after brain‐death induction were heterotopically transplanted into C57BL/6 recipients. We demonstrate that, in line with our in vitro studies, M1/Mdivi1 pretreatment protected cardiac allografts from injury, decreased infiltrating T cell production of cytotoxic proteins, and prolonged allograft survival. Collectively, our data show promoting mitochondrial fusion in donor ECs mitigates recipient T cell responses and leads to significantly improved cardiac transplant survival.

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Expression of Mitochondrial-Encoded Genes in Blood Differentiate Acute Renal Allograft Rejection

Cited by 8 publications

References 26 publications

Donor plasma mitochondrial DNA is associated with antibody-mediated rejection in renal allograft recipients

Donor plasma mitochondrial DNA is associated with antibody-mediated rejection in renal allograft recipients

Hypoglycemic, anti‐inflammatory, and neuroprotective potentials of crude methanolic extract from Acacia nilotica L. – results of an in vitro study

Modulating donor mitochondrial fusion/fission delivers immunoprotective effects in cardiac transplantation

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