TY - JOUR
T1 - Molecular Mechanisms of Epigenetic Regulation, Inflammation, and Cell Death in ADPKD
AU - Agborbesong, Ewud
AU - Li, Linda Xiaoyan
AU - Li, Lu
AU - Li, Xiaogang
N1 - Publisher Copyright:
Copyright © 2022 Agborbesong, Li, Li and Li.
PY - 2022/6/29
Y1 - 2022/6/29
N2 - Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder, which is caused by mutations in the PKD1 and PKD2 genes, characterizing by progressive growth of multiple cysts in the kidneys, eventually leading to end-stage kidney disease (ESKD) and requiring renal replacement therapy. In addition, studies indicate that disease progression is as a result of a combination of factors. Understanding the molecular mechanisms, therefore, should facilitate the development of precise therapeutic strategies for ADPKD treatment. The roles of epigenetic modulation, interstitial inflammation, and regulated cell death have recently become the focuses in ADPKD. Different epigenetic regulators, and the presence of inflammatory markers detectable even before cyst growth, have been linked to cyst progression. Moreover, the infiltration of inflammatory cells, such as macrophages and T cells, have been associated with cyst growth and deteriorating renal function in humans and PKD animal models. There is evidence supporting a direct role of the PKD gene mutations to the regulation of epigenetic mechanisms and inflammatory response in ADPKD. In addition, the role of regulated cell death, including apoptosis, autophagy and ferroptosis, have been investigated in ADPKD. However, there is no consensus whether cell death promotes or delays cyst growth in ADPKD. It is therefore necessary to develop an interactive picture between PKD gene mutations, the epigenome, inflammation, and cell death to understand why inherited PKD gene mutations in patients may result in the dysregulation of these processes that increase the progression of renal cyst formation.
AB - Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder, which is caused by mutations in the PKD1 and PKD2 genes, characterizing by progressive growth of multiple cysts in the kidneys, eventually leading to end-stage kidney disease (ESKD) and requiring renal replacement therapy. In addition, studies indicate that disease progression is as a result of a combination of factors. Understanding the molecular mechanisms, therefore, should facilitate the development of precise therapeutic strategies for ADPKD treatment. The roles of epigenetic modulation, interstitial inflammation, and regulated cell death have recently become the focuses in ADPKD. Different epigenetic regulators, and the presence of inflammatory markers detectable even before cyst growth, have been linked to cyst progression. Moreover, the infiltration of inflammatory cells, such as macrophages and T cells, have been associated with cyst growth and deteriorating renal function in humans and PKD animal models. There is evidence supporting a direct role of the PKD gene mutations to the regulation of epigenetic mechanisms and inflammatory response in ADPKD. In addition, the role of regulated cell death, including apoptosis, autophagy and ferroptosis, have been investigated in ADPKD. However, there is no consensus whether cell death promotes or delays cyst growth in ADPKD. It is therefore necessary to develop an interactive picture between PKD gene mutations, the epigenome, inflammation, and cell death to understand why inherited PKD gene mutations in patients may result in the dysregulation of these processes that increase the progression of renal cyst formation.
KW - ADPKD
KW - cell death
KW - epigenetics
KW - inflammation
KW - post-translational modifications
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U2 - 10.3389/fmolb.2022.922428
DO - 10.3389/fmolb.2022.922428
M3 - Review article
AN - SCOPUS:85134175621
SN - 2296-889X
VL - 9
JO - Frontiers in Molecular Biosciences
JF - Frontiers in Molecular Biosciences
M1 - 922428
ER -