Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: Ischemia reperfusion injury (IRI) is an inevitable event in conventional organ transplant procedure and affects the prognosis in post-transplantation. Increasing evidence suggests that microRNA plays a vital role in regulation of IRI. Our previous research has proven that down-regulation of let-7 can improve liver regeneration after series of injury. However the role of let7 on liver IRI remains unclear. We aim to explore the role of let-7 on the common process and the underlining mechanism.
*Methods: LO2 and AML12 Cell lines hypoxia-reoxygenation(H/R) was established to mimic the liver IRI process in vitro. The expression of let-7 family in IRI was studied in vivo and in vitro in 0h, 1h, 6h and 24h after reoxygenation, we also test the expression level of let-7 family in 10 pairs of clinical samples from the donor liver after IRI. Then we constructed LV-let-7b LO2 cell line. qRT-PCR and Western Blot were used to detect expression level of JAK-STAT pathway and SOCS in mRNA and protein level respectively. Dual-luciferase reporter was performed in HEK293cells to identify the mechanism of let-7b regulating SOCS3.
*Results: The results of LO2 hypoxia-reoxygenation injury model and clinical tissues shows the significant downregulation of let-7b in IRI (fig.1). Up-regulation of let-7b improved active oxygen rate and reduced cell viability significantly indicating that down regulation of let-7b may have protective effect on IRI. The expression of p-STAT3 was decreased in correspondence with let-7b. At the same time, expression of SOCS3 was up-regulated. Dual-luciferase reporter showed that let-7b can bind to 3’UTR of SOCS3 (fig.2).
*Conclusions: Downregulation of let-7b may protect hepatic tissues from IRI by increasing the expression of SOCS3 which can inhibit JAK-STAT3 pathway. Our next step is to validate this regulatory pathway of let-7b in transgenic mice 70%IRI model.
To cite this abstract in AMA style:Sun C, Hou Y, Huang S, Wu L. Protection Role of microRNA let-7 in Hepatic Ischemia Reperfusion Injury by Inhibiting JAK-STAT3 Pathway [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/protection-role-of-microrna-let-7-in-hepatic-ischemia-reperfusion-injury-by-inhibiting-jak-stat3-pathway/. Accessed December 4, 2020.
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