Abstract: FR-PO0186
Integrin α5β1 Protect from AKI-to-CKD Transition Through Inhibiting Tubular Epithelial Cell Autophagy
Session Information
- AKI: Mechanisms - 2
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Author
- Yu, Yanting, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, Nanjing, Jiangsu, China
Background
The mechanism of AKI transit to CKD is unclear. We hypothesized integrin α5β1 were involved in the process through autophagy and regulated by microRNA(miR)-19-3p.
Methods
Cisplatin (9mg/kg) was intraperitoneally injected to male C57BL/6J mice once a week for 4 times and terminated at day 24 to bild AKI-CKD model. Integrin α5β1 plasmid or inhibitor (ATN-161) was administrated to the model mice, and tested the level of Scr, BUN, LC3, Atg5 and PI3K-Akt-mTOR signaling pathway. In vitro, the HK-2 cell was stimulated with integrin α5β1 plasmid or ATN-161, and the expression of FN, a-SMA, LC-3β and Atg5 were examined. Inhibitor or mimic of miR-19-3p was given to normal mice or model mice, to explore the effect of miR-19-3p and the relationship with integrin α5β1. In vitro, the HK-2 cell was stimulated with mimic or inhibitor of miR-19-3p. Ultimately, the model mice were given 3-methyladenine (3-MA) (20mg/kg, i.p.) for 7 consective days from day 17 to day 23 to explore the role of autophagy.
Results
In low-dose multiple cisplatin treated mice, the Scr and BUN were elevated significantly, the protein expression of FN and a-SMA were significantly increased, and as the same as fibrosis degree in kidney tissue. In model mice, integrin α5β1 was decreased in kidney tissue, but miR-19-3p was elevated. Transfecting plasmid to overexpress integrin α5β1 in model mice, the elevated Scr, BUN and FN and a-SMA decreased. Atg5 and LC-3β were decreased. The pPI3K/PI3K, pAKT/AKT, and p-mTOR/mTOR was suppressed in cisplatin stimulation, and was improved after overexpress integrin α5β1. When normal mice were administrated with ATN-161 to inhibit integrin α5β1 expression, the Scr level and a-SMA expression was increased. Pretreated with inhibitor of miR-19-3p in cisplatin induced mice, led to recovery of kidney function and kidney damage. The elevated protein expression of Atg5 was also decreased. However, miR-19-3p mimics lowered integrin α5β1 expression significantly in HK-2 cells in vitro, and the inhibitor increased integrin α5β1 expression. At last, 3-MA treated with cisplatin suppressed autophagy and restore Scr, BUN, FN and a-SMA expression, but not integrin α5β1.
Conclusion
Integrin α5β1 protect from cisplatin induced AKI to CKD transition by inhibiting autophagy, which through PI3K-Akt-mTOR signaling pathway, and negative regulated by miR-19-3p.
Funding
- Government Support – Non-U.S.