Yupeng Chen

Oct 29, 2024 | translational-medicine.biomedcentral.com | Jiayi Lv |Lili Fu |Chenchen Zhou |Yupeng Chen |Changlin Mei |Cheng Xue | +5 more

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a prevalent genetic disorder characterized by the formation of renal cysts leading to kidney failure. Despite known genetic underpinnings, the variability in disease progression suggests additional regulatory layers, including epigenetic modifications. We utilized various ADPKD models, including Pkd1 and Ezh2 conditional knockout (Pkd1delta/delta:Ezh2delta/delta) mice, to explore the role of Enhancer of Zeste Homolog 2 (EZH2) in cystogenesis. Pharmacological inhibition of EZH2 was performed using GSK126 or EPZ-6438 across multiple models. EZH2 expression was significantly upregulated in Pkd1−/− cells, Pkd1delta/delta mice, and human ADPKD kidneys. EZH2 inhibition attenuates cyst development in MDCK cells and a mouse embryonic kidney cyst model. Both Ezh2 conditional knockout and GSK126 treatment suppressed renal cyst growth and protected renal function in Pkd1delta/delta mice. Mechanistically, cAMP/PKA/CREB pathway increased EZH2 expression. EZH2 mediated cystogenesis by enhancing methylation and activation of STAT3, promoting cell cycle through p21 suppression, and stimulating non-phosphorylated β-catenin in Wnt signaling pathway. Additionally, EZH2 enhanced ferroptosis by inhibiting SLC7A11 and GPX4 in ADPKD. Our findings elucidate the pivotal role of EZH2 in promoting renal cyst growth through epigenetic mechanisms and suggest that EZH2 inhibition or ablation may serve as a novel therapeutic approach for managing ADPKD.

Mar 30, 2024 | onlinelibrary.wiley.com | Lili Wang |Yuhui Zhang |Yupeng Chen |Lei Jiang

Conflict of Interest The authors declare no conflict of interest. Supporting Information Filename Description adfm202401411-sup-0001-SuppMat.pdf975 KB Supporting Information References 1, , , , Exploration 2021, 1, 20210101. 2, Chem. Soc. Rev. 2010, 39, 901. 3, , , , , , , Chem. Soc. Rev. 2023, 52, 6270. 4, , , , , , , Nat. Commun. 2021, 12, 1573. 5, , , , , , , , , , , , Nat. Protoc. 2021, 16, 4201. 6, , , Chem. Soc. Rev. 2011, 40, 2385. 7, , , , ACS Nano 2023, 17, 24539.

Dec 20, 2023 | dx.doi.org | Lili Wang |Yuhui Zhang |Yupeng Chen |Lei Jiang

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Aug 30, 2023 | dx.doi.org | Yutian Ma |Shiyao Li |Xin Lin |Yupeng Chen

Ribonucleic acid (RNA)-based therapies have become an attractive topic in disease intervention, especially with some that have been approved by the FDA such as the mRNA COVID-19 vaccine (Comirnaty, Pfizer-BioNTech, and Spikevax, Moderna) and Patisiran (siRNA-based drug for liver delivery). However, extensive applications are still facing challenges in delivering highly negatively charged RNA to the targeted site.