Multifunctional Applications of Extracellular Nanovesicles for Acute Kidney Injury and Renal Fibrosis; a Mini Review

Extracellular vesicles (EVs) are released into body fluids, including blood, urine, saliva, pleural and peritoneal fluid, by various cell types through different mechanisms. Various types of EVs differ in structure and function; but, their common characteristic is carrying a variety of bioactive molecules such as RNA, proteins, and lipids. EVs can regulate the function of target cells through interaction with them. Acute kidney injury (AKI) is a common and potentially serious clinical condition characterized by a rapid decline in renal function, manifested as abnormal classic indicators such as serum creatinine and decreased urine output. AKI not only affects the renal function of patients, but it is also closely related to dysfunction in other organs, including the lung, heart, brain, liver, intestine, and immune system. EVs by carrying bioactive molecules (eg, proteins, RNA, lipids) and mediating intercellular communication can play critical roles in inflammation, apoptosis, tubular injury, and fibrosis during AKI. Some key mechanisms of EVs in AKI pathophysiology include promoting tubular cell proliferation, enriching HMGB1/HSP70, leading to NF-Kβ/MAPK activation, and carrying pro-inflammatory molecules (eg, TNF-α, IL-1β, IL-6). In the context of renal fibrosis, EVs can directly participate in its pathogenesis by carrying pro-fibrotic factors and regulating fibroblast activity, accelerating the progression of fibrosis. Besides being involved in the pathogenesis, EVs can also serve as potential diagnostic tools and therapeutic agents against AKI and renal fibrosis. This narrative review summarizes the biogenesis, composition, and functional mechanisms of EVs in AKI as well as renal fibrosis pathogenesis, along with highlighting their potential as diagnostic biomarkers and therapeutic targets.