DNA Methylation Sustains “Inflamed” Memory of Peripheral Immune Cells Aggravating Kidney Inflammatory Response in Chronic Kidney Disease

Chen, Xiaojun; Zhang, Hong; Yang, Fei; Liu, Yu; Chen, Guochun

doi:10.3389/fphys.2021.637480

Cited by 10 publications

(11 citation statements)

References 111 publications

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“…The results of studies point out chronic inflammation as a factor implicated in the pathogenesis of various diseases, including CKD [21,22]. Inflammation also contributes to the progression of this disease [23]. The finding of diffuse interstitial infiltration of neutrophils, T lymphocytes, B lymphocytes, and monocytes within the kidney seems to confirm the importance of the aforementioned process.…”

Section: Chronic Kidney Diseasementioning

confidence: 88%

“…The biological mechanisms related to CKD and its progression remain elusive [7]. Currently, the treatment of chronic kidney disease involves the management of common abnormalities, including proteinuria, hyperglycemia, hypertension, etc., however, in some patients these measures are not sufficient and thus they progress to end-stage renal disease (ESRD) [23]. Genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS) have identified frequent variants within more than >400 genetic loci that are associated with renal function and the development of CKD [27][28][29][30].…”

Section: Chronic Kidney Diseasementioning

confidence: 99%

“…The methylation of DNA reversibly affects gene expression without modifying DNA sequence [32,33]. DNA methylation-related transcriptional downregulation was suggested to be associated with hampering the interaction between transcription factors and their targets as well as with the recruitment of specific transcriptional repressors to the methylated DNA [23]. Apart from being involved in the silencing of transposable elements, X-chromosome inactivation and imprinting, DNA methylation is a powerful tool responsible for transcriptional silencing.…”

Section: Dna Methylationmentioning

confidence: 99%

“…In such a manner, uremic "memory" is established [43,44]. The results of studies have demonstrated that epigenetic "memory" of the earlier trigger can be maintained for a long time and modulate the forthcoming gene expression profile [23]. A complex system comprising epigenetic regulators and transcription factors regulates altered gene expression in CKD [20].…”

Section: Dna Methylation In Ckdmentioning

confidence: 99%

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Are Alterations in DNA Methylation Related to CKD Development?

Rysz

Franczyk

Rysz-Górzyńska

et al. 2022

IJMS

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The modifications in genomic DNA methylation are involved in the regulation of normal and pathological cellular processes. The epigenetic regulation stimulates biological plasticity as an adaptive response to variations in environmental factors. The role of epigenetic changes is vital for the development of some diseases, including atherogenesis, cancers, and chronic kidney disease (CKD). The results of studies presented in this review have suggested that altered DNA methylation can modulate the expression of pro-inflammatory and pro-fibrotic genes, as well those essential for kidney development and function, thus stimulating renal disease progression. Abnormally increased homocysteine, hypoxia, and inflammation have been suggested to alter epigenetic regulation of gene expression in CKD. Studies of renal samples have demonstrated the relationship between variations in DNA methylation and fibrosis and variations in estimated glomerular filtration rate (eGFR) in human CKD. The unravelling of the genetic–epigenetic profile would enhance our understanding of processes underlying the development of CKD. The understanding of multifaceted relationship between DNA methylation, genes expression, and disease development and progression could improve the ability to identify individuals at risk of CKD and enable the choice of appropriate disease management.

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Section: Chronic Kidney Diseasementioning

confidence: 88%

Section: Chronic Kidney Diseasementioning

confidence: 99%

Section: Dna Methylationmentioning

confidence: 99%

Section: Dna Methylation In Ckdmentioning

confidence: 99%

See 2 more Smart Citations

Are Alterations in DNA Methylation Related to CKD Development?

Rysz

Franczyk

Rysz-Górzyńska

et al. 2022

IJMS

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“…In this context, T cell dysregulation due to prolonged exposure of exogenous pathogens promotes the pro-inflammatory phenotype of multiple effector cells, which migrate into the involved kidneys remote from the original infection site and contribute to persistent inflammatory tissue injury (24,25). Importantly, the "inflamed" phenotype of peripheral T cells might sustain for a long time and affect the tissue inflammatory homeostasis after they migrate from the circulation into the involved kidney (26). Therefore, physicians need to comprehensively assess the clinical significance of T cell-mediated crosstalk among immune cells and consider the therapeutic potentials of targeting T cell activity in CKD progression with a timing-specific manner.…”

Section: The Rationale Of Targeting T Cell Dysregulation In Chronic Kidney Inflammation Upon Infectionmentioning

confidence: 99%

An Emerging Role of TIM3 Expression on T Cells in Chronic Kidney Inflammation

Lü¹,

Chen

Wang

et al. 2022

Front. Immunol.

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T cell immunoglobulin domain and mucin domain 3 (TIM3) was initially identified as an inhibitory molecule on IFNγ-producing T cells. Further research discovered the broad expression of TIM3 on different immune cells binding to multiple ligands. Apart from its suppressive effects on the Th1 cells, recent compelling experiments highlighted the indispensable role of TIM3 in the myeloid cell-mediated inflammatory response, supporting that TIM3 exerts pleiotropic effects on both adaptive and innate immune cells in a context-dependent manner. A large number of studies have been conducted on TIM3 biology in the disease settings of infection, cancer, and autoimmunity. However, there is a lack of clinical evidence to closely evaluate the role of T cell-expressing TIM3 in the pathogenesis of chronic kidney disease (CKD). Here, we reported an intriguing case of Mycobacterium tuberculosis (Mtb) infection that was characterized by persistent overexpression of TIM3 on circulating T cells and ongoing kidney tubulointerstitial inflammation for a period of 12 months. In this case, multiple histopathological biopsies revealed a massive accumulation of recruited T cells and macrophages in the enlarged kidney and liver. After standard anti-Mtb treatment, repeated renal biopsy identified a dramatic remission of the infiltrated immune cells in the tubulointerstitial compartment. This is the first clinical report to reveal a time-course expression of TIM3 on the T cells, which is pathologically associated with the progression of severe kidney inflammation in a non-autoimmunity setting. Based on this case, we summarize the recent findings on TIM3 biology and propose a novel model of CKD progression due to the aberrant crosstalk among immune cells.

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Epigenetic regulation of mitochondrial‐endoplasmic reticulum dynamics in kidney diseases

Shelke,

Yelgonde,

Kale

et al. 2023

Journal Cellular Physiology

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Kidney diseases are serious health problems affecting >800 million individuals worldwide. The high number of affected individuals and the severe consequences of kidney dysfunction demand an intensified effort toward more effective prevention and treatment. The pathophysiology of kidney diseases is complex and comprises diverse organelle dysfunctions including mitochondria and endoplasmic reticulum (ER). The recent findings prove interactions between the ER membrane and nearly all cell compartments and give new insights into molecular events involved in cellular mechanisms in health and disease. Interactions between the ER and mitochondrial membranes, known as the mitochondria‐ER contacts regulate kidney physiology by interacting with each other via membrane contact sites (MCS). ER controls mitochondrial dynamics through ER stress sensor proteins or by direct communication via mitochondria‐associated ER membrane to activate signaling pathways such as apoptosis, calcium transport, and autophagy. More importantly, these organelle dynamics are found to be regulated by several epigenetic mechanisms such as DNA methylation, histone modifications, and noncoding RNAs and can be a potential therapeutic target against kidney diseases. However, a thorough understanding of the role of epigenetic regulation of organelle dynamics and their functions is not well understood. Therefore, this review will unveil the role of epigenetic mechanisms in regulating organelle dynamics during various types of kidney diseases. Moreover, we will also shed light on different stress origins in organelles leading to kidney disease. Henceforth, by understanding this we can target epigenetic mechanisms to maintain/control organelle dynamics and serve them as a novel therapeutic approach against kidney diseases.

show abstract

DNA Methylation Sustains “Inflamed” Memory of Peripheral Immune Cells Aggravating Kidney Inflammatory Response in Chronic Kidney Disease

Cited by 10 publications

References 111 publications

Are Alterations in DNA Methylation Related to CKD Development?

Are Alterations in DNA Methylation Related to CKD Development?

An Emerging Role of TIM3 Expression on T Cells in Chronic Kidney Inflammation

Epigenetic regulation of mitochondrial‐endoplasmic reticulum dynamics in kidney diseases

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