Abstract: TH-PO221
Long Noncoding RNA ENST00000436340 Promotes Podocyte Injury of Diabetic Kidney Disease by Facilitating the Association of PTBP1 With RAB3B
Session Information
- Diabetic Kidney Disease: Basic - I
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Lv, Zhimei, Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Hu, Jinxiu, Department of Nephrology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Wang, Rong, Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
Background
Dysfunction and injury of podocytes has been regarded as an early pathologic characteristic of diabetic kidney disease (DKD), but the role of long noncoding RNAs in this process remains largely unknown.By performing RNA sequencing, we identified ENST00000436340 was significantly upregulated in DKD. However, its function and detailed molecular mechanisms are undefined.
Methods
real-time PCR was performed to verify ENST00000436340 expression in DKD. Spearman correlation analysis were used to evaluate the correlation between ENST00000436340 and kidney function. real-time PCR, WB, Immunofluorescence, and FITC-phalloidin staining were performed to assess the lesion of podocyte. MeRIP was performed to investigate the underlying mechanism of ENST00000436340 upregulation. FISH and subcellular fractionation assays were conducted to identify the localization of ENST00000436340 in podocytes. RNA pulldown, RIP and serial deletions assay were performed to explore the interaction between ENST00000436340, RAB3B and PTBP1.
Results
We discovered ENST00000436340 was upregulated in DKD, and we showed a correlation between upregulated ENST00000436340 and the severity of kidney injury. Function experiments showed that silencing of ENST00000436340 alleviated high glucose-induced podocyte injury and cytoskeleton rearrangement. Mechanistically, we showed that FTO-mediated m6A induced the upregulation of ENST00000436340, which interacted with PTBP1 and augmented PTBP1 binding to RAB3B mRNA, promoted RAB3B mRNA degradation, and thereby caused cytoskeleton rearrangement and inhibition of GLUT4 translocation, leading to podocyte injury.
Conclusion
We identified an ENST00000436340-PTBP1-RAB3B axis in regulating cytoskeleton rearrangement and GLUT4 translocation, leading to podocyte injury, which will provide insights into the prevent and treatment of DKD in the future.
Funding
- Government Support – Non-U.S.