miR-142-5p Encapsulated by Serum-Derived Extracellular Vesicles Protects against Acute Lung Injury in Septic Rats following Remote Ischemic Preconditioning via the PTEN/PI3K/Akt Axis

Abstract

This study intends to investigate the effects of miR-142-5p encapsulated by serum-derived extracellular vesicles (EVs) on septic acute lung injury (ALI) following remote ischemic preconditioning (RIPC) through a PTEN-involved mechanism. ALI was induced in rats by lipopolysaccharide (LPS) injection, 24 h before which RIPC was performed via the left lower limb. Next, the binding affinity between miR-142-5p and PTEN was identified. EVs were isolated from serum and injected into rats. The morphology of lung tissues, pulmonary edema, and inflammatory cell infiltration into lung tissues were then assessed, and TNF-α and IL-6 levels in serum and lung tissues were measured. The results indicated that RIPC could attenuate ALI in sepsis. miR-142-5p expression was increased in serum, lung tissues, and serum-derived EVs of ALI rats following RIPC. miR-142-5p could target PTEN to activate the PI3K/Akt signaling pathway. miR-142-5p shuttled by serum-derived EVs reduced pulmonary edema, neutrophil infiltration, and TNF-α and IL-6 levels, thus alleviating ALI in LPS-induced septic rats upon RIPC. Collectively, serum-derived EVs-loaded miR-142-5p downregulated PTEN and activated PI3K/Akt to inhibit ALI in sepsis following RIPC, thus highlighting potential therapeutic molecular targets against ALI in sepsis.

Research hotspots and frontiers of preconditioning in cerebral ischemia: A bibliometric analysis

“…RIPC successfully induces ischemic tolerance not only in the brain, but also in the heart [ 151 ], kidneys [ 152 ], lungs [ 153 ], and liver [ 154 ], which seems to suggest that repeated ischemic preconditioning of one artery may have induced ischemic tolerance throughout the body. How does this protective effect extend from local to other areas?…”

How Extracellular Nano-Vesicles Can Play a Role in Sepsis? An Evidence-Based Review of the Literature

“…85 Zhu et al used the same pretreatment strategy as Pan et al and found miR-142-5p reduced the level of pro-inflammatory factors and neutrophil infiltration, it also relieved pulmonary oedema via the PTEN/PI3K/Akt axis. 86 In addition, ADMSC subjected to hypoxic preconditioning promoted mmu_circ_0001295 expression in Exos, which attenuated renal vascular leakage and inflammation in kidney and improved kidney function. Early clinical intervention may improve outcomes and reduce the mortality of patients with sepsis.…”

Harnessing Extracellular microRNAs for Diagnostics and Therapeutics in Acute Systemic Inflammation

“…Thus, miRNAs can affect cellular functions beyond the scope of the intracellular posttranscriptional modifications, which they were originally discovered to perform three decades ago [ 1 ]. This expanded understanding of miRNAs has helped reveal their role in acute inflammation, providing new opportunities to explore treatments of immune dysregulation, particularly in sepsis [ 10 , 49 , 50 ]. This section of the review will focus on the activity of extracellular miRNAs in vesicles and bound by proteins.…”

“…Another miRNA, miR-142-5p, can travel inside extracellular vesicles to bind with and inhibit phosphatase and tensin homolog (PTEN) activity, thus promoting phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) activity [ 50 ]. In a mouse model of cecal ligation and puncture (CLP)-induced sepsis, exosomal miR-93-5p inhibited lysine-specific demethylase 6B (KDM6B) , reducing TNF-α production and acute kidney injury (AKI) [ 75 ].…”