Citation: Yujie Zhu, Ruijianghan Shi, Weitong Lu, Yang Chen, Yunfeng Lin, Sirong Shi. Tetrahedral framework nucleic acids prevent epithelial-mesenchymal transition-mediated diabetic fibrosis by targeting the Wnt/β-catenin signaling pathway[J]. Chinese Chemical Letters, ;2025, 36(5): 110140. doi: 10.1016/j.cclet.2024.110140 shu

Tetrahedral framework nucleic acids prevent epithelial-mesenchymal transition-mediated diabetic fibrosis by targeting the Wnt/β-catenin signaling pathway

Yujie Zhu ^{a, b} ,
Ruijianghan Shi ^{a, b} ,
Weitong Lu ^{a, b} ,
Yang Chen ^c ,
Yunfeng Lin ^{a, b} ,
Sirong Shi ^{a, b, *,}

a.
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
b.
Sichuan Provincial Engineering Research Center of Oral Biomaterials, Chengdu 610041, China
c.
Department of Pediatric Surgery, Department of Liver Surgery & Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, China

sirongshi@scu.edu.cn

Received Date: 3 April 2024
Revised Date: 16 June 2024
Accepted Date: 18 June 2024
Available Online: 19 June 2024

Figures(4)

Diabetic kidney disease (DKD) is recognized as a severe complication in the development of diabetes mellitus (DM), posing a significant burden for global health. Major characteristics of DKD kidneys include tubulointerstitial oxidative stress, inflammation, excessive extracellular matrix deposition, and progressing renal fibrosis. However, current treatment options are limited and cannot offer enough efficacy, thus urgently requiring novel therapeutic approaches. Tetrahedral framework nucleic acids (tFNAs) are a novel type of self-assembled DNA nanomaterial with excellent structural stability, biocompatibility, tailorable functionality, and regulatory effects on cellular behaviors. In this study, we established an in vitro high glucose (HG)-induced human renal tubular epithelial cells (HK-2 cells) pro-fibrogenic model and explored the antioxidative, anti-inflammatory, and antifibrotic capacity of tFNAs and the potential molecular mechanisms. tFNAs not only effectively alleviated oxidative stress through reactive oxygen species (ROS)-scavenging and activating the serine and threonine kinase (Akt)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway but also inhibited the production of pro-inflammatory factors such as tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in diabetic HK-2 cells. Additionally, tFNAs significantly downregulated the expression of Collagen I and α-smooth muscle actin (α-SMA), two representative biomarkers of pro-fibrogenic myofibroblasts in the renal tubular epithelial-mesenchymal transition (EMT). Furthermore, we found that tFNAs exerted this function by inhibiting the Wnt/β-catenin signaling pathway, preventing the occurrence of EMT and fibrosis. The findings of this study demonstrated that tFNAs are naturally endowed with great potential to prevent fibrosis progress in DKD kidneys and can be further combined with emerging pharmacotherapies, providing a secure and efficient drug delivery strategy for future DKD therapy.
- Tetrahedral framework nucleic acids,
- DNA nanomaterials,
- Diabetic kidney disease,
- Renal fibrosis,
- Antifibrotic therapy
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