Mecp2 protects kidney from ischemia-reperfusion injury through transcriptional repressing IL-6/STAT3 signaling

Wang, Jiao; Xiong, Mingrui; Fan, Yadong; Liu, Chengyu; Wang, Qing; Yang, Dong; Yuan, Yangmian; Huang, Yixue; Wang, Shun; Niu, Shu-Xuan; Yue, Junqiu; Su, Hua; Zhang, Chun; Chen, Hong; Zheng, Ling; Huang, Kun

doi:10.7150/thno.72515

Cited by 29 publications

(16 citation statements)

References 65 publications

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“…To verify this conjecture, we further used exogenous IL-6 to intervene in APN rats. The results also showed that an activating IL-6/STAT3 axis could promote the pathological process of APN, which was consistent with former studies (27). However, the accelerated pathological process of APN caused by the IL-6/STAT3 axis was completely reversed by CX extract, confirming the regulatory relationship between them.…”

Section: Discussionsupporting

confidence: 91%

Szechwan Lovage Rhizome Extract Improves Renal Function and Alleviates Inflammatory Responses in Pyelonephritis Rats Infected with Escherichia Coli via IL-6/STAT3 Axis

José¹,

Bi²,

Liu³

et al. 2023

Cell Mol Biol (Noisy-le-grand)

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Section: Discussionsupporting

confidence: 91%

Szechwan Lovage Rhizome Extract Improves Renal Function and Alleviates Inflammatory Responses in Pyelonephritis Rats Infected with Escherichia Coli via IL-6/STAT3 Axis

José¹,

Bi²,

Liu³

et al. 2023

Cell Mol Biol (Noisy-le-grand)

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“…It has been documented that MeCP2 can regulate the transcription of FOXO3a by methylating its promoter region, thus influencing cellular functions 58 . MeCP2 binds to the promoter of pro‐inflammatory cytokine II‐6 and negatively regulates its expression in ischemia‐reperfusion injury of the kidney 59 . Here, we found that SPESP1 can bind to the MBD of MeCP2 to reduce hypermethylation of the DCN promoter region.…”

Section: Discussionmentioning

confidence: 61%

Downregulated SPESP1‐driven fibroblast senescence decreases wound healing in aged mice

Zhong,

Zhou,

Guo

et al. 2024

Clinical & Translational Med

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BackgroundHuman dermal fibroblasts (HDFs) are essential in the processes of skin ageing and wound healing. However, the underlying mechanism of HDFs in skin healing of the elderly has not been well defined. This study aims to elucidate the mechanisms of HDFs senescence and how senescent HDFs affect wound healing in aged skin.MethodsThe expression and function of sperm equatorial segment protein 1 (SPESP1) in skin ageing were evaluated via in vivo and in vitro experiments. To delve into the potential molecular mechanisms by which SPESP1 influences skin ageing, a combination of techniques was employed, including proteomics, RNA sequencing, immunoprecipitation, chromatin immunoprecipitation and liquid chromatography‐mass spectrometry analyses. Clearance of senescent cells by dasatinib plus quercetin (D+Q) was investigated to explore the role of SPESP1‐induced senescent HDFs in wound healing.ResultsHere, we define the critical role of SPESP1 in ameliorating HDFs senescence and retarding the skin ageing process. Mechanistic studies demonstrate that SPESP1 directly binds to methyl‐binding protein, leading to Decorin demethylation and subsequently upregulation of its expression. Moreover, SPESP1 knockdown delays wound healing in young mice and SPESP1 overexpression induces wound healing in old mice. Notably, pharmacogenetic clearance of senescent cells by D+Q improved wound healing in SPESP1 knockdown skin.ConclusionsTaken together, these findings reveal the critical role of SPESP1 in skin ageing and wound healing, expecting to facilitate the development of anti‐ageing strategies and improve wound healing in the elderly.

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“…Mouse primary tubular epithelial cells were isolated from renal cortex of C57BL/6 mice as previously reported (Wang et al , 2022a). Briefly, minced renal cortex was digested using 1 mg/ml type II collagenase (Sigma‐Aldrich), then sequentially passed through 200‐μm and 70‐μm cell strainers, followed by culturing in RPMI‐1640 medium with 5 mg/l human epidermal growth factor (PeproTech, Rocky Hill, NJ) for further experiments.…”

Section: Methodsmentioning

confidence: 99%

Loss of renal tubular G9a benefits acute kidney injury by lowering focal lipid accumulation via CES1

et al. 2023

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Surgery-induced renal ischemia and reperfusion (I/R) injury and nephrotoxic drugs like cisplatin can cause acute kidney injury (AKI), for which there is no effective therapy. Lipid accumulation is evident following AKI in renal tubules although the mechanisms and pathological effects are unclear. Here, we report that Ehmt2-encoded histone methyltransferase G9a is upregulated in patients and mouse kidneys after AKI. Renal tubular specific knockout of G9a (Ehmt2 Ksp ) or pharmacological inhibition of G9a alleviates lipid accumulation associated with AKI. Mechanistically, G9a suppresses transcription of the lipolytic enzyme Ces1; moreover, G9a and farnesoid X receptor (FXR) competitively bind to the same promoter regions of Ces1. Ces1 is consistently observed to be downregulated in the kidney of AKI patients. Pharmacological inhibition of Ces1 increases lipid accumulation, exacerbates renal I/R-injury and eliminates the beneficial effects on AKI observed in Ehmt2 Ksp mice. Furthermore, lipid-lowering atorvastatin and an FXR agonist alleviate AKI by activating Ces1 and reducing renal lipid accumulation. Together, our results reveal a G9a/FXR-Ces1 axis that affects the AKI outcome via regulating renal lipid accumulation.

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Mecp2 protects kidney from ischemia-reperfusion injury through transcriptional repressing IL-6/STAT3 signaling

Cited by 29 publications

References 65 publications

Szechwan Lovage Rhizome Extract Improves Renal Function and Alleviates Inflammatory Responses in Pyelonephritis Rats Infected with Escherichia Coli via IL-6/STAT3 Axis

Szechwan Lovage Rhizome Extract Improves Renal Function and Alleviates Inflammatory Responses in Pyelonephritis Rats Infected with Escherichia Coli via IL-6/STAT3 Axis

Downregulated SPESP1‐driven fibroblast senescence decreases wound healing in aged mice

Loss of renal tubular G9a benefits acute kidney injury by lowering focal lipid accumulation via CES1

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