Icariin Attenuates Human Renal Tubular Epithelial Cell Senescence by Targeting PAK2 via miR-23b-3p

Title:Icariin Attenuates Human Renal Tubular Epithelial Cell Senescence by Targeting PAK2 via miR-23b-3p

Volume: 25 Issue: 17

Author(s): Suqin Zhang*, Yanbin Li and Qiuyue Wang

Affiliation:

• Department of Traditional Chinese Medicine, Shanghai Eighth People's Hospital, Shanghai, 200235, China

Keywords: Diabetic kidney disease, Icariin, senescence, exosomal micro-RNA, PAK2, miR-23b-3p, renal tubular epithelial cells.

Abstract:

Background: Renal tubular epithelial cells (RTECs) senescence is crucial in kidney diseases. Icariin is shown to have protective effects against renal fibrosis, acute kidney injury, and proteinuria. We aimed to explore the role of icariin in protecting RTECs from senescence and the underlying mechanism involved.

Methods: An in vitro model of RTEC senescence was established by incubating HK-2 cells with urine exosomes from patients with diabetic kidney disease. Stimulated cells were treated with icariin at various doses to evaluate the compound's therapeutic effects. After RNA transfection, cell cycle arrest and senescence, flow cytometry, and SA-β-Gal staining were analyzed. At the same time, quantitative real-time PCR examined microRNA expression. Biochemical assays.

Results: Urine exosomes induced senescence and cell cycle arrest in the G1 stage in HK-2 cells, which were inhibited by icariin. Urine exosome stimulation up-regulated miR-23b-3p expression, which in turn suppressed PAK2 expression. Significantly, the induced and inhibited miR- 23b-3p expressions weakened and augmented the resistance of cells against urine exosome stimulation, respectively, while PAK2 overexpression provided additional protection. Icariin suppressed miR-23b-3p expression, and miR-23b-3p induction blocked the effects of icariin and promoted RTEC senescence.

Conclusion: miR-23b-3p and PAK2 form a signaling axis that regulates RTEC senescence upon urine exosome stimulation. Icariin can increase the resistance of RTECs against senescence via miR-23b-3p/PAK2. Our findings shed light on the mechanism of the clinical effects of icariin on renal diseases, which can be exploited to develop effective drugs targeting RTEC senescence in the future.

Cite this article as:

Zhang Suqin*, Li Yanbin and Wang Qiuyue, Icariin Attenuates Human Renal Tubular Epithelial Cell Senescence by Targeting PAK2 via miR-23b-3p, Current Pharmaceutical Biotechnology 2024; 25 (17) . https://dx.doi.org/10.2174/0113892010276372231129105022