scholarly journals MicroRNA Expression Changes in Kidney Transplant: Diagnostic Efficacy of miR-150-5p as Potential Rejection Biomarker, Pilot Study

2021 ◽  
Vol 10 (13) ◽  
pp. 2748
Author(s):  
Rafael Alfaro ◽  
Isabel Legaz ◽  
Victor Jimenez-Coll ◽  
Jaouad El kaaoui El band ◽  
Helios Martínez-Banaclocha ◽  
...  

Background: The kidney allograft biopsy is considered the gold standard for rejection diagnosis but is invasive and could be indeterminate. Several publications point to the role of miRNA expression in suggesting its involvement in the acceptance or rejection of organ transplantation. This study aimed to analyze microRNAs involved in the differentiation and activation of B and T lymphocytes from kidney transplant (KT) patients’ peripheral blood leukocytes to be used as biomarkers of acute renal rejection (AR). Methods: A total of 15 KT patients with and without acute rejection (AR/NAR) were analyzed and quantified by miRNA PCR array. A total of 84 miRNAs related to lymphocyte differentiation and activation B and T were studied. The functions and biological pathways were analyzed to predict the potential targets of differential expressed miRNAs. Results: Six miRNA were increased in the AR group (miR-191-5p, miR-223-3p, miR-346, miR-423-5p, miR-574-3p, and miR-181d) and miR-150-5p was increased in the NAR group. In silico studies showed a total of 2603 target genes for the increased miRNAs in AR, while for the decrease miRNA, a total of 1107 target-potential genes were found. Conclusions: Our results show that KT with AR shows a decrease in miR-150-5p expression compared to NAR, suggesting that the decrease in miR-150-5p could be related to an increased MBD6 whose deregulation could have clinical consequences.

2020 ◽  
Vol 11 ◽  
Author(s):  
Joohyun Park ◽  
Ji Young Chang ◽  
Jong Youl Kim ◽  
Jong Eun Lee

The immune response following neuroinflammation is a vital element of ischemic stroke pathophysiology. After the onset of ischemic stroke, a specialized vasculature system that effectively protects central nervous system tissues from the invasion of blood cells and other macromolecules is broken down within minutes, thereby triggering the inflammation cascade, including the infiltration of peripheral blood leukocytes. In this series of processes, blood-derived monocytes have a significant effect on the outcome of ischemic stroke through neuroinflammatory responses. As neuroinflammation is a necessary and pivotal component of the reparative process after ischemic stroke, understanding the role of infiltrating monocytes in the modulation of inflammatory responses may offer a great opportunity to explore new therapies for ischemic stroke. In this review, we discuss and highlight the function and involvement of monocytes in the brain after ischemic injury, as well as their impact on tissue damage and repair.


1999 ◽  
Vol 5 (12) ◽  
pp. 812-819 ◽  
Author(s):  
M. Djavad Mossalayi ◽  
Pierre-André Becherel ◽  
Patrice Debré

2020 ◽  
Author(s):  
Yi Yang ◽  
Ran Luo ◽  
Yichun Cheng ◽  
Tingting Liu ◽  
Wei Dai ◽  
...  

Abstract Background Increased leucine-rich α2-glycoprotein-1 (LRG1) has been observed in various inflammatory and autoimmune diseases. We aimed to explore the expression and role of LRG1 in lupus nephritis (LN). Methods Plasma LRG1 (pLRG1) was measured by enzyme-linked immunosorbent assay in 101 patients with renal biopsy-proven LN and 21 healthy controls (HC). Relationships between pLRG1 and clinical and pathological characteristics were analyzed. The expression of LRG1 in peripheral blood leukocytes and kidney was detected by flow cytometry, immunohistochemistry and immunofluorescence, respectively. Further cell experiments were focused on the role of LRG1. Results We found that LRG1 was expressed in plasma, some peripheral blood leukocytes, proximal tubule and several inflammatory cells. The levels of LRG1 in plasma, peripheral blood leukocytes and kidney were elevated in LN patients as compared to HC. Plasma expression levels of LRG1 correlated positively with renal function and renal disease activity, and reflect specific pathologic lesions in the kidneys of patients with LN. Interleukin-1β and interleukin-6, not tumor necrosis factor-α and interferon γ induced the LRG1 expression in human renal tubular epithelial cell line. Moreover, stimulation of recombinant human LRG1 could inhibit late apoptosis, promote proliferation and regulate expression of inflammatory factors and cytokines. Conclusions Plasma expression levels of LRG1 were associated with renal function, disease activity, and pathology in LN. It might also be involved in renal inflammation, proliferation and apoptosis of endothelial cells. LRG1 might be a potential prognosis novel predictor in LN patients.


Epigenomics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 873-888 ◽  
Author(s):  
Luca Parrillo ◽  
Rosa Spinelli ◽  
Michele Longo ◽  
Antonella Desiderio ◽  
Paola Mirra ◽  
...  

Aim: First-degree relatives (FDR) of individuals with Type 2 diabetes (T2D) feature restricted adipogenesis, which render them more vulnerable to T2D. Epigenetics may contribute to these abnormalities. Methods: FDR pre-adipocyte Methylome and Transcriptome were investigated by MeDIP- and RNA-Seq, respectively. Results: Methylome analysis revealed 2841 differentially methylated regions (DMR) in FDR. Most DMR localized into gene-body and were hypomethylated. The strongest hypomethylation signal was identified in an intronic-DMR at the PTPRD gene. PTPRD hypomethylation in FDR was confirmed by bisulphite sequencing and was responsible for its upregulation. Interestingly, Ptprd-overexpression in 3T3-L1 pre-adipocytes inhibited adipogenesis. Notably, the validated PTPRD-associated DMR was significantly hypomethylated in peripheral blood leukocytes from the same FDR individuals. Finally, PTPRD methylation pattern was also replicated in obese individuals. Conclusion: Our findings indicated a previously unrecognized role of PTPRD in restraining adipogenesis. This abnormality may contribute to increase FDR proclivity toward T2D.


2021 ◽  
Vol 22 (12) ◽  
pp. 6491
Author(s):  
Giulia Chinetti ◽  
Jaap G. Neels

Vascular calcification is defined as an inappropriate accumulation of calcium depots occurring in soft tissues, including the vascular wall. Growing evidence suggests that vascular calcification is an actively regulated process, sharing similar mechanisms with bone formation, implicating both inhibitory and inducible factors, mediated by osteoclast-like and osteoblast-like cells, respectively. This process, which occurs in nearly all the arterial beds and in both the medial and intimal layers, mainly involves vascular smooth muscle cells. In the vascular wall, calcification can have different clinical consequences, depending on the pattern, localization and nature of calcium deposition. Nuclear receptors are transcription factors widely expressed, activated by specific ligands that control the expression of target genes involved in a multitude of pathophysiological processes, including metabolism, cancer, inflammation and cell differentiation. Some of them act as drug targets. In this review we describe and discuss the role of different nuclear receptors in the control of vascular calcification.


2001 ◽  
Vol 49 (4) ◽  
pp. 473-478
Author(s):  
J. Iqbal ◽  
A. S. Purewal ◽  
N. Edington

The aim of this study was to investigate the role of immediate early gene (gene63) in the pathogenesis of equine herpesvirus 1 (EHV-1) acute and latent infections in equine and murine models. EHV-1 gene63 mutant virus (g63mut) along with EHV-1 (Ab4) was used for intracerebral and intranasal infection of 3 and 17-day-old mice. Both viruses were recovered at the same frequency from tissues after infection. Two Welsh ponies were infected via the intranasal route with each of the viruses. Acute infection was monitored by virus isolation from nasal swabs and peripheral blood leukocytes. Six weeks post infection, peripheral blood leukocytes were taken from ponies and in vitro reactivation was positive for both viruses. At autopsy, both viruses were isolated by co-cultivation from bronchial and submandibular lymph nodes. These findings indicate that the mutation of EHV-1 gene63 does not play a role in the establishment and reactivation from latency.


2020 ◽  
Author(s):  
Yi Yang ◽  
Ran Luo ◽  
Yichun Cheng ◽  
Tingting Liu ◽  
Wei Dai ◽  
...  

Abstract Background Increased leucine-rich α2-glycoprotein-1 (LRG1) has been observed in various inflammatory and autoimmune diseases. We aimed to explore the expression and role of LRG1 in lupus nephritis (LN). Methods Plasma LRG1 (pLRG1) was measured by enzyme-linked immunosorbent assay in 101 patients with renal biopsy-proven LN and 21 healthy controls (HC). Relationships between pLRG1 and clinical and pathological characteristics were analyzed. The expression of LRG1 in peripheral blood leukocytes and kidney was detected by flow cytometry, immunohistochemistry and immunofluorescence, respectively. Further cell experiments were focused on the role of LRG1. Results We found that LRG1 was expressed in plasma, some peripheral blood leukocytes, proximal tubule and several inflammatory cells. The levels of LRG1 in plasma, peripheral blood leukocytes and kidney were elevated in LN patients as compared to HC. Plasma expression levels of LRG1 correlated positively with renal function and renal disease activity, and reflect specific pathologic lesions in the kidneys of patients with LN. Interleukin-1β and interleukin-6, not tumor necrosis factor-α and interferon γ induced the LRG1 expression in human renal tubular epithelial cell line. Moreover, stimulation of recombinant human LRG1 could inhibit late apoptosis, promote proliferation and regulate expression of inflammatory factors and cytokines. Conclusions Plasma expression levels of LRG1 were associated with renal function, disease activity, and pathology in LN. It might also be involved in renal inflammation, proliferation and apoptosis of endothelial cells. LRG1 might be a potential prognosis novel predictor in LN patients.


1974 ◽  
Vol 22 (1) ◽  
pp. 46-50 ◽  
Author(s):  
LAWRENCE KASS ◽  
BERTRAM SCHNITZER

A cytochemical technique was devised for demonstrating a lysosomal enzyme capable of hydrolyzing histone. The test for histonase involved incubation of peripheral blood leukocytes in a mixture of calf thymus histone (substrate) and Fe(NH4)2(SO4)2·6H2O. Combination of this iron salt occurred with products of histone cleavage (arginine, lysine, glycine). The iron-amino acid complex was made visible in the cytoplasm of the cell by the Prussian blue stain. Histonase enzyme was found to have a narrow substrate specificity and to react only with histone and not with a variety of biologic and synthetic substrates for protease activity. The role of histonase in the transfer of information from nucleus to cytoplasm is discussed.


2019 ◽  
Author(s):  
Yi Yang ◽  
Ran Luo ◽  
Yichun Cheng ◽  
Tingting Liu ◽  
Wei Dai ◽  
...  

Abstract Background Increased leucine-rich α2-glycoprotein-1 (LRG1) has been observed in various inflammatory and autoimmune diseases. We aimed to explore the expression and role of LRG1 in lupus nephritis (LN).Methods Plasma LRG1 (pLRG1) was measured by enzyme-linked immunosorbent assay in 101 patients with renal biopsy-proven LN and 21 healthy controls (HC). Relationships between pLRG1 and clinical and pathological characteristics were analyzed. The expression of LRG1 in peripheral blood leukocytes and kidney was detected by flow cytometry, immunohistochemistry and immunofluorescence, respectively. Further cell experiments were focused on the role of LRG1.Results We found that LRG1 was expressed in plasma, some peripheral blood leukocytes, proximal tubule and several inflammatory cells. The levels of LRG1 in plasma, peripheral blood leukocytes and kidney were elevated in LN patients as compared to HC. Plasma expression levels of LRG1 correlated positively with renal function and renal disease activity, and reflect specific pathologic lesions in the kidneys of patients with LN. Interleukin-1β and interleukin-6, not tumor necrosis factor-α and interferon γ induced the LRG1 expression in human renal tubular epithelial cell line. Moreover, stimulation of recombinant human LRG1 could inhibit late apoptosis, promote proliferation and regulate expression of inflammatory factors and cytokines.Conclusions Plasma expression levels of LRG1 were associated with renal function, disease activity, and pathology in LN. It might also be involved in renal inflammation, proliferation and apoptosis of endothelial cells. LRG1 might be a potential prognosis novel predictor in LN patients.


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