The Role and Mechanism of Lysine Methyltransferase and Arginine Methyltransferase in Kidney Diseases

Zhou, Xun; Chen, Hui; Li, Jinqing; Shi, Yingfeng; Zhuang, Songlin; Liu, Na

doi:10.3389/fphar.2022.885527

Cited by 5 publications

(3 citation statements)

References 78 publications

(103 reference statements)

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“…EZH2, a histone-lysine N-methyltransferase enzyme, has been identified as an important therapeutic target to treat renal tubulointerstitial fibrosis (16). EZH2 is up-regulated in several animal models of renal fibrosis and pharmaceutically inhibition of EZH2 ameliorates renal tubulointerstitial fibrosis (17). Recent study showed that EZH2 is a direct target of triptolide and thus we hypothesized that triptolide inhibits renal fibrosis by targeting EZH2.…”

Section: Discussionmentioning

confidence: 99%

Triptolide ameliorates renal tubulointerstitial fibrosis through EZH2

Wang

Jing²,

Huang

et al. 2023

Preprint

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Renal fibrosis is the final pathological pathway of various kidney disease in progression to the end stage of renal failure. Recent studies showed that the histone methyltransferase enhancer of zeste homolog 2 (EZH2) is an important epigenetic regulator of renal fibrosis by promoting epithelial-mesenchymal transition (EMT) and activation of TGF-β/Smad3 signaling pathway in fibrotic kidneys. Triptolide is component extracted from radix tripterygium wilfordii, which provides renal benefits to patients with renal diseases in China. Recently, triptolide was identified as an inhibitor of EZH2. Thus, we hypothesized that triptolide inhibits renal fibrosis through EZH2. In this study, we found that triptolide reduced the deposition of extracellular matrix in the kidney of unilateral ureteral obstruction (UUO) mice. The anti-fibrotic effect of triptolide was further confirmed in TGF-β stimulated HK2 cells, a human renal epithelial cell line. Moreover, treatment of triptolide blocked the up-regulation of EZH2 in UUO kidneys and reduced the expression of EZH2 in TGF-β stimulated HK2 cells. Down-regulation of EZH2 by triptolide was correlated with reduced expression of EMT markers and phosphorylation of Smad3 in UUO kidneys and TGF-β stimulated HK2 cells. Finally, we showed that inhibition of EZH2 by 3-DZNep attenuated the inhibitory effect of triptolide on the expression of extracellular matrix protein, EMT markers and activation of Smad3 in TGF-β stimulated HK2 cells. In conclusion, triptolide inhibits renal tubulointerstitial fibrosis through EZH2 in obstructive kidneys.

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Section: Discussionmentioning

confidence: 99%

Triptolide ameliorates renal tubulointerstitial fibrosis through EZH2

Wang

Jing²,

Huang

et al. 2023

Preprint

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“…Histone methylation refers to the transfer of up to three methyl groups from the common methyl donor S‐adenosyl‐L‐methionine (SAM) to lysine or arginine residues of histones (Horiuchi et al., 2013 ; Rungratanawanich et al., 2023 ). Histone methyltransferases can be generally classified into three different classes: SET domain‐containing N‐lysine methyltransferases, disruptor of telomeric silencing 1‐like (DOT1L) with lysine as its substrate, and protein arginine transferases (PRMTs) which result in methylation of arginine (Horiuchi et al., 2013 ; Zhou et al., 2022 ). According to the products generated, all PRMTs can be divided into two subtypes: Type I PRMTs, including PRMT1, 3, and 4 that generate asymmetric dimethylarginine; and Type II PRMTs, including PRMT 5 and 7 that generate symmetric dimethylarginine.…”

Section: How Do Hallmarks Of Aging Participate In the Pathogenesis Of...mentioning

confidence: 99%

Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging

Wang,

Yuan,

Wang

et al. 2024

Aging Cell

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Osteoarthritis (OA), a chronic degenerative joint disease, is highly prevalent among the aging population, and often leads to joint pain, disability, and a diminished quality of life. Although considerable research has been conducted, the precise molecular mechanisms propelling OA pathogenesis continue to be elusive, thereby impeding the development of effective therapeutics. Notably, recent studies have revealed subchondral bone lesions precede cartilage degeneration in the early stage of OA. This development is marked by escalated osteoclast‐mediated bone resorption, subsequent imbalances in bone metabolism, accelerated bone turnover, and a decrease in bone volume, thereby contributing significantly to the pathological changes. While the role of aging hallmarks in OA has been extensively elucidated from the perspective of chondrocytes, their connection with osteoclasts is not yet fully understood. There is compelling evidence to suggest that age‐related abnormalities such as epigenetic alterations, proteostasis network disruption, cellular senescence, and mitochondrial dysfunction, can stimulate osteoclast activity. This review intends to systematically discuss how aging hallmarks contribute to OA pathogenesis, placing particular emphasis on the age‐induced shifts in osteoclast activity. It also aims to stimulate future studies probing into the pathological mechanisms and therapeutic approaches targeting osteoclasts in OA during aging.

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“…731 PRMT and PKMT can not only catalyze the methylation of histones, but also catalyze the methylation of nonhis-tone proteins. 732 For example, the DNA damage response proteins MRE11 and 53BP1 can be methylated by PRMT1 to regulate its DNA exonuclease activity and localization at DNA damage sites. 733 Some immunomodulatory proteins, such as Vav1 and NIP45, can also be modified by arginine methylation.…”

Section: Methylationmentioning

confidence: 99%

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Zhong

Xiao

Xie

et al. 2023

MedComm

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Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on the backbones or amino acid side chains of proteins and expand the diversity of proteins, which provides the basis for the emergence of organismal complexity. To date, more than 650 types of protein modifications, such as the most well‐known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short‐chain and long‐chain acylation modifications, redox modifications, and irreversible modifications, have been described, and the inventory is still increasing. By changing the protein conformation, localization, activity, stability, charges, and interactions with other biomolecules, PTMs ultimately alter the phenotypes and biological processes of cells. The homeostasis of protein modifications is important to human health. Abnormal PTMs may cause changes in protein properties and loss of protein functions, which are closely related to the occurrence and development of various diseases. In this review, we systematically introduce the characteristics, regulatory mechanisms, and functions of various PTMs in health and diseases. In addition, the therapeutic prospects in various diseases by targeting PTMs and associated regulatory enzymes are also summarized. This work will deepen the understanding of protein modifications in health and diseases and promote the discovery of diagnostic and prognostic markers and drug targets for diseases.

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The Role and Mechanism of Lysine Methyltransferase and Arginine Methyltransferase in Kidney Diseases

Cited by 5 publications

References 78 publications

Triptolide ameliorates renal tubulointerstitial fibrosis through EZH2

Triptolide ameliorates renal tubulointerstitial fibrosis through EZH2

Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

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