Potential targeted therapy and diagnosis based on novel insight into growth factors, receptors, and downstream effectors in acute kidney injury and acute kidney injury-chronic kidney disease progression

摘要

Acute kidney injury (AKI) is defined as a rapid decline in renal function and is characterized by excessive renal inflammation andprogrammed death of resident cells. AKI shows high morbidity and mortality, and severe or repeated AKI can transition to chronickidney disease (CKD) or even end-stage renal disease (ESRD); however, very few effective and specific therapies are available,except for supportive treatment. Growth factors, such as epidermal growth factor (EGF), insulin-like growth factor (IGF), andtransforming growth factor-β (TGF-β), are significantly altered in AKI models and have been suggested to play critical roles in therepair process of AKI because of their roles in cell regeneration and renal repair. In recent years, a series of studies have shownevidence that growth factors, receptors, and downstream effectors may be highly involved in the mechanism of AKI and mayfunction in the early stage of AKI in response to stimuli by regulating inflammation and programmed cell death. Moreover, certaingrowth factors or correlated proteins act as biomarkers for AKI due to their sensitivity and specificity. Furthermore, growth factorsoriginating from mesenchymal stem cells (MSCs) via paracrine signaling or extracellular vesicles recruit leukocytes or repair intrinsiccells and may participate in AKI repair or the AKI-CKD transition. In addition, growth factor-modified MSCs show superiortherapeutic potential compared to that of unmodified controls. In this review, we summarized the current therapeutic anddiagnostic strategies targeting growth factors to treat AKI in clinical trials. We also evaluated the possibilities of other growth factorcorrelatedmolecules as therapeutic targets in the treatment of AKI and the AKI-CKD transition.