Hsa-miR-494-3p attenuates gene HtrA3 transcription to increase inflammatory response in hypoxia/reoxygenation HK2 Cells

Abstract

The occurrence of cardiac surgery-associated acute kidney injury (CSA-AKI) increases hospital stay and mortality. MicroRNAs has a crucial role in AKI. This objective of the current study is to explore the function of hsa-miR-494-3p in inflammatory response in human kidney tubular epithelial (HK2) cells with hypoxia/reoxygenation. According to KDIGO standard, patients after cardiac surgery with cardiopulmonary bypass were divided into two groups: AKI (n = 10) and non-AKI patients (n = 8). HK2 were raised in the normal and hypoxia/reoxygenation circumstances and mainly treated by overexpression ofmiR-494-3p and HtrA3. The relationship between miR-494-3p and HtrA3 was determined by dual-luciferase reporter assay. Our result showed that Hsa-miR-494-3p was elevated in the serum of patients with CSA-AKI, and also induced in hypoxic reoxygenated HK2 cells. Hsa-miR-494-3p also increased a hypoxia-reoxygenation induced inflammatory response in HK2 cells. Moreover, as a target gene of miR-494-3p, overexpression of HtrA3 downregulated the hypoxia-reoxygenation induced inflammatory response in HK2 cells. Overexpression of hsa-miR-494-3p-induced inflammatory response was inhibited by overexpression of HtrA3. Collectively, we identified that hsa-miR-494-3p, a miRNA induced in both circulation of AKI patients and hypoxia-reoxygenation-treated HK2 cells, enhanced renal inflammation by targeting HtrA3, which may suggest a possible role as a new therapeutic target for CSA-AKI.

Rat Bone Mesenchymal Stem Cell‐Derived Exosomes Loaded with miR‐494 Promoting Neurofilament Regeneration and Behavioral Function Recovery after Spinal Cord Injury

“…miR-494 refers to a tumor suppressor inhibiting the proliferation and colony formation of tumor cells [ 30 ]. miR-494 can reduce autophagy and apoptosis of PC-12 cells induced by LPS by targeting IL-13 in vitro [ 18 ].…”

Epithelium-derived exosomes promote silica nanoparticles-induced pulmonary fibroblast activation and collagen deposition via modulating fibrotic signaling pathways and their epigenetic regulations

“…As manifested in previous studies, exposure to particles resulted in lung injury and fibrogenesis by modulating miR-494-3p, miR-21, and miR-96 [ 73 – 75 ]. Of note, miR-494-3p has been known to mediate multi-disease processes, as manifested by enhancing inflammatory response [ 76 ], increasing cell proliferation and migration [ 77 ], and cellular senescence [ 78 ]. Moreover, EVs derived from lung fibroblasts from patients with pulmonary fibrosis were rich in miR-494-3p, which could accelerate epithelial phenotypic changes [ 63 ].…”

mmu-lncRNA 121686/hsa-lncRNA 520657 induced by METTL3 drive the progression of AKI by targeting miR-328-5p/HtrA3 signaling axis

“… 23 , 27 , 28 , 29 , 30 In addition, a study reported that HtrA3 suppressed the hypoxia-reoxygenation-induced inflammation response. 31 However, whether HtrA3 can induce renal cell apoptosis has not been discovered yet during ischemic injury. The results demonstrated that the deletion of HtrA3 attenuated BUMPT and HK-2 cell apoptosis during ATP-depletion injury ( Figure 8 ), thereby supporting its pro-apoptotic role.…”