Epigenetic memory contributing to the pathogenesis of AKI-to-CKD transition

Abstract

Epigenetic memory, which refers to the ability of cells to retain and transmit epigenetic marks to their daughter cells, maintains unique gene expression patterns. Establishing programmed epigenetic memory at each stage of development is required for cell differentiation. Moreover, accumulating evidence shows that epigenetic memory acquired in response to environmental stimuli may be associated with diverse diseases. In the field of kidney diseases, the “memory” of acute kidney injury (AKI) leads to progression to chronic kidney disease (CKD); epidemiological studies show that patients who recover from AKI are at high risk of developing CKD. The underlying pathological processes include nephron loss, maladaptive epithelial repair, inflammation, and endothelial injury with vascular rarefaction. Further, epigenetic alterations may contribute as well to the pathophysiology of this AKI-to-CKD transition. Epigenetic changes induced by AKI, which can be recorded in cells, exert long-term effects as epigenetic memory. Considering the latest findings on the molecular basis of epigenetic memory and the pathophysiology of AKI-to-CKD transition, we propose here that epigenetic memory contributing to AKI-to-CKD transition can be classified according to the presence or absence of persistent changes in the associated regulation of gene expression, which we designate “driving” memory and “priming” memory, respectively. “Driving” memory, which persistently alters the regulation of gene expression, may contribute to disease progression by activating fibrogenic genes or inhibiting renoprotective genes. This process may be involved in generating the proinflammatory and profibrotic phenotypes of maladaptively repaired tubular cells after kidney injury. “Priming” memory is stored in seemingly successfully repaired tubular cells in the absence of detectable persistent phenotypic changes, which may enhance a subsequent transcriptional response to the second stimulus. This type of memory may contribute to AKI-to-CKD transition through the cumulative effects of enhanced expression of profibrotic genes required for wound repair after recurrent AKI. Further understanding of epigenetic memory will identify therapeutic targets of future epigenetic intervention to prevent AKI-to-CKD transition.

Intravitreal ranibizumab injection is associated with an increased risk of chronic kidney disease: a population-based study in Taiwan

“…Acute kidney injury and CKD are intercorrelated (Okusa et al 2009 ; Coca et al 2012 ). Notably, patients recovering from acute kidney injury may be at risk of CKD due to nephron loss, incomplete repair, inflammation, fibrosis, and epigenetic changes (Wang and Zhang 2022 ; Tanemoto et al 2022 ). As our study lacked serial clinical and laboratory parameters, such as blood pressure or urine protein levels, further prospective studies are needed to examine the causality and time course of the association between intravitreal VEGF inhibitors and risk of CKD.…”

Environmental determinants of health of the population of Ukrainian regions in the context of sustainable development

“…responsible for the most important functions of synthesis of essential proteins, ion transport, an increase in copies of genes encoding essential proteins, and others. New structures are formed, which increases the functional capacity of the system and brings the organism to a new level of functioning required for the duration of the environmental factor (Chu et al, 2022;Tanemoto et al, 2022). The number of newly created structures is called the "structural cost of adaptation".…”

“…This pathogenetic mechanism is called local wear and tear of the systems dominant in adaptation. All of these mechanisms are characteristic of long-term exposure to radiation (Chu et al, 2022;Tanemoto et al, 2022).…”

The Role of Hypoxia on the Trimethylation of H3K27 in Podocytes

“…Kroening et al [ 33 ] showed that hypoxia reduces the expression of CTGF (connective tissue growth factor, a stimulator of extra cellular matrix) in human kidney epithelial cells with the involvement of DNA methylation [ 33 ]. Some publications describe a so-called hypoxic memory that drives the transition of acute kidney injury (AKI) to CKDs [ 34 , 35 ]. Epidemiological studies showed that even after AKI, a certain percentage of patients who recovered from AKI develop CKD [ 34 , 35 ].…”

“…Some publications describe a so-called hypoxic memory that drives the transition of acute kidney injury (AKI) to CKDs [ 34 , 35 ]. Epidemiological studies showed that even after AKI, a certain percentage of patients who recovered from AKI develop CKD [ 34 , 35 ]. Therefore, renal hypoxia can also induce the establishment of cellular memory.…”