MiR-342-5p Alleviates Inflammatory Responses in Sepsis-Induced AKI by Targeting PFN1

Abstract

Background: The development of several human diseases has been linked to microRNA-342-5p (miR-342-5p). However, its specific function in the inflammatory reactions associated with sepsis-triggered acute kidney injury (AKI) remains unexplored. This study aims to delve into the role of miR-342-5p in the progression of sepsis-induced AKI. Methods: To understand the underlying mechanism of miR-342-5p in sepsis, we established sepsis models through induction with lipopolysaccharide (LPS). The cell proliferation and apoptosis were assessed using the 5-ethynyl-2′-deoxyuridine (EdU) method and flow cytometry, respectively. Bioinformatics analysis was employed to predict the downstream binding target of miR-342-5p, and their interaction was confirmed through a dual-luciferase reporter gene assay. The rescue tests were conducted to further explore the action pathway of miR-342-5p. Results: The administration of LPS significantly decreased the HK2 cell proliferation (p < 0.05), and increased cell apoptosis. Additionally, there was a notable downregulation in miR-342-5p expression accompanied by an elevated level of inflammatory factor (p < 0.05). Furthermore, the overexpression of miR-342-5p effectively attenuated the LPS-induced inflammatory response in HK2 cells (p < 0.05). Profilin-1 (PFN1) emerged as a pivotal player in sepsis pathogenesis, serving as a critical downstream target of miR-342-5p. Interestingly, rescue experiments demonstrated that the stimulatory effects of miR-342-5p mimics were counteracted by the overexpression of PFN1 in sepsis. Conclusions: MiR-342-5p alleviates inflammatory responses in sepsis by targeting PFN1.