Abstract 50: Abrogation of stromal TGF-β signaling induces DNA damage and genetic/epigenetic alterations in neighboring epithelia

2012 ◽  
Author(s):  
B. Achyut ◽  
David A. Bader ◽  
Yanli Pang ◽  
Curtis C. Harris ◽  
Li Yang
Keyword(s):  
Dna Damage ◽  
Epigenetic Alterations

scholarly journals Epigenetic Alterations in Podocytes in Diabetic Nephropathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Erina Sugita ◽  
Kaori Hayashi ◽  
Akihito Hishikawa ◽  
Hiroshi Itoh
Keyword(s):  
Dna Damage ◽  
Diabetic Nephropathy ◽  
Epigenetic Changes ◽  
Epigenetic Alterations ◽  
Human Samples ◽  
Differentiated Cells ◽  
Damage Repair ◽  
Patients With Diabetes ◽  
Stage Renal Disease ◽  
End Stage

Recently, epigenetic alterations have been shown to be involved in the pathogenesis of diabetes and its complications. Kidney podocytes, which are glomerular epithelial cells, are important cells that form a slit membrane—a barrier for proteinuria. Podocytes are terminally differentiated cells without cell division or replenishment abilities. Therefore, podocyte damage is suggested to be one of the key factors determining renal prognosis. Recent studies, including ours, suggest that epigenetic changes in podocytes are associated with chronic kidney disease, including diabetic nephropathy. Furthermore, the association between DNA damage repair and epigenetic changes in diabetic podocytes has been demonstrated. Detection of podocyte DNA damage and epigenetic changes using human samples, such as kidney biopsy and urine-derived cells, may be a promising strategy for estimating kidney damage and renal prognoses in patients with diabetes. Targeting epigenetic podocyte changes and associated DNA damage may become a novel therapeutic strategy for preventing progression to end-stage renal disease (ESRD) and provide a possible prognostic marker in diabetic nephropathy. This review summarizes recent advances regarding epigenetic changes, especially DNA methylation, in podocytes in diabetic nephropathy and addresses detection of these alterations in human samples. Additionally, we focused on DNA damage, which is increased under high-glucose conditions and associated with the generation of epigenetic changes in podocytes. Furthermore, epigenetic memory in diabetes is discussed. Understanding the role of epigenetic changes in podocytes in diabetic nephropathy may be of great importance considering the increasing diabetic nephropathy patient population in an aging society.

Pathophysiological changes of ageing and their relevance to anaesthesia

2017 ◽  
Author(s):  
Chris Dodds ◽  
Chandra M. Kumar ◽  
Frédérique Servin
Keyword(s):  
Dna Damage ◽  
Genome Instability ◽  
Organ System ◽  
Epigenetic Alterations ◽  
Functional Reserve ◽  
Behavioural Adaptation ◽  
Mitochondrial Dna Damage ◽  
Specific Organ ◽  
Systemic Problems ◽  
Musculoskeletal Systems

The molecular basis of ageing is reviewed. This includes the concept of a summation of DNA damage over a lifetime causing genome instability. Epigenetic alterations, telomeric shortening, and the possibility of their modification are discussed. Oxidative and mitochondrial DNA damage and the resulting dysfunction leading to senescence are briefly described. Systemic problems and resultant behavioural adaptation may mask the decline in functional reserve and cause some of the difficulties in identifying its presence in ill elderly patients. Specific organ system changes are then described in some detail. These include the major concerns with the cardiovascular, respiratory, renal, hepatic, neurologic, endocrine, and musculoskeletal systems. The effect of ageing on the special senses of vision and hearing are covered, with emphasis on issues of informed consent.

scholarly journals DNA Oncogenic Virus-Induced Oxidative Stress, Genomic Damage, and Aberrant Epigenetic Alterations

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Mankgopo Magdeline Kgatle ◽  
Catherine Wendy Spearman ◽  
Asgar Ali Kalla ◽  
Henry Norman Hairwadzi
Keyword(s):  
Dna Damage ◽  
Oncogenic Viruses ◽  
Epigenetic Alterations ◽  
Ongoing Research ◽  
Genomic Changes ◽  
Barr Virus ◽  
Genome Wide ◽  
Genomic Damage ◽  
Epstein Barr ◽  
Underlying Mechanisms

Approximately 20% of human cancers is attributable to DNA oncogenic viruses such as human papillomavirus (HPV), hepatitis B virus (HBV), and Epstein-Barr virus (EBV). Unrepaired DNA damage is the most common and overlapping feature of these DNA oncogenic viruses and a source of genomic instability and tumour development. Sustained DNA damage results from unceasing production of reactive oxygen species and activation of inflammasome cascades that trigger genomic changes and increased propensity of epigenetic alterations. Accumulation of epigenetic alterations may interfere with genome-wide cellular signalling machineries and promote malignant transformation leading to cancer development. Untangling and understanding the underlying mechanisms that promote these detrimental effects remain the major objectives for ongoing research and hope for effective virus-induced cancer therapy. Here, we review current literature with an emphasis on how DNA damage influences HPV, HVB, and EBV replication and epigenetic alterations that are associated with carcinogenesis.

scholarly journals Altered DNA methylation in kidney disease: useful markers and therapeutic targets

2022 ◽  
Author(s):  
Kaori Hayashi
Keyword(s):  
Dna Methylation ◽  
Dna Damage ◽  
Dna Repair ◽  
Kidney Disease ◽  
Environmental Changes ◽  
Therapeutic Targets ◽  
Epigenetic Mechanism ◽  
Epigenetic Changes ◽  
Epigenetic Alterations ◽  
Lifestyle Related Diseases

AbstractRecent studies have demonstrated the association of altered epigenomes with lifestyle-related diseases. Epigenetic regulation promotes biological plasticity in response to environmental changes, and such plasticity may cause a ‘memory effect’, a sustained effect of transient treatment or an insult in the course of lifestyle-related diseases. We investigated the significance of epigenetic changes in several genes required for renal integrity, including the nephrin gene in podocytes, and the sustained anti-proteinuric effect, focusing on the transcription factor Krüppel-like factor 4 (KLF4). We further reported the role of the DNA repair factor lysine-acetyl transferase 5 (KAT5), which acts coordinately with KLF4, in podocyte injury caused by a hyperglycemic state through the acceleration of DNA damage and epigenetic alteration. In contrast, KAT5 in proximal tubular cells prevents acute kidney injury via glomerular filtration regulation by an epigenetic mechanism as well as promotion of DNA repair, indicating the cell type-specific action and roles of DNA repair factors. This review summarizes epigenetic alterations in kidney diseases, especially DNA methylation, and their utility as markers and potential therapeutic targets. Focusing on transcription factors or DNA damage repair factors associated with epigenetic changes may be meaningful due to their cell-specific expression or action. We believe that a better understanding of epigenetic alterations in the kidney will lead to the development of a novel strategy for chronic kidney disease (CKD) treatment.

scholarly journals Retrotransposons as a Source of DNA Damage in Neurodegeneration

2022 ◽  
Vol 13 ◽  
Author(s):  
Eugenie Peze-Heidsieck ◽  
Tom Bonnifet ◽  
Rania Znaidi ◽  
Camille Ravel-Godreuil ◽  
Olivia Massiani-Beaudoin ◽  
...  
Keyword(s):  
Dna Damage ◽  
Repetitive Sequences ◽  
Potential Contribution ◽  
Epigenetic Alterations ◽  
Human Dna ◽  
Mammalian Genomes ◽  
Disease Modifying ◽  
Long Interspersed Element ◽  
Coding Potential ◽  
Novel Therapeutic

The etiology of aging-associated neurodegenerative diseases (NDs), such as Parkinson’s disease (PD) and Alzheimer’s disease (AD), still remains elusive and no curative treatment is available. Age is the major risk factor for PD and AD, but the molecular link between aging and neurodegeneration is not fully understood. Aging is defined by several hallmarks, some of which partially overlap with pathways implicated in NDs. Recent evidence suggests that aging-associated epigenetic alterations can lead to the derepression of the LINE-1 (Long Interspersed Element-1) family of transposable elements (TEs) and that this derepression might have important implications in the pathogenesis of NDs. Almost half of the human DNA is composed of repetitive sequences derived from TEs and TE mobility participated in shaping the mammalian genomes during evolution. Although most TEs are mutated and no longer mobile, more than 100 LINE-1 elements have retained their full coding potential in humans and are thus retrotransposition competent. Uncontrolled activation of TEs has now been reported in various models of neurodegeneration and in diseased human brain tissues. We will discuss in this review the potential contribution of LINE-1 elements in inducing DNA damage and genomic instability, which are emerging pathological features in NDs. TEs might represent an important molecular link between aging and neurodegeneration, and a potential target for urgently needed novel therapeutic disease-modifying interventions.

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