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

Abstract

Acute kidney injury (AKI) is defined as a rapid decline in renal function and is characterized by excessive renal inflammation and programmed death of resident cells. AKI shows high morbidity and mortality, and severe or repeated AKI can transition to chronic kidney 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), and transforming growth factor-β (TGF-β), are significantly altered in AKI models and have been suggested to play critical roles in the repair process of AKI because of their roles in cell regeneration and renal repair. In recent years, a series of studies have shown evidence that growth factors, receptors, and downstream effectors may be highly involved in the mechanism of AKI and may function in the early stage of AKI in response to stimuli by regulating inflammation and programmed cell death. Moreover, certain growth factors or correlated proteins act as biomarkers for AKI due to their sensitivity and specificity. Furthermore, growth factors originating from mesenchymal stem cells (MSCs) via paracrine signaling or extracellular vesicles recruit leukocytes or repair intrinsic cells and may participate in AKI repair or the AKI-CKD transition. In addition, growth factor-modified MSCs show superior therapeutic potential compared to that of unmodified controls. In this review, we summarized the current therapeutic and diagnostic strategies targeting growth factors to treat AKI in clinical trials. We also evaluated the possibilities of other growth factorcorrelated molecules as therapeutic targets in the treatment of AKI and the AKI-CKD transition.

The immune system as a target for therapy of SARS-CoV-2: A systematic review of the current immunotherapies for COVID-19

“…Cell-based therapies have been used to management of several illnesses including pulmonary [ [109] , [110] , [111] ], cardiovascular [ 112 , 113 ], hepatic [ 114 ], and renal [ 115 ] diseases. Also, the safety and effectiveness of the treatment with stem cells have been documented in many clinical trials, especially in immune-mediated inflammatory diseases, such as SLE and graft-versus-host disease (GVHD) [ 110 , 116 ].…”

Mesenchymal Stromal Cell Uses for Acute Kidney Injury—Current Available Data and Future Perspectives: A Mini-Review

“…In the AKI setting, growth factors also play a role by regulating inflammation and programmed cell death. When administrated early after the acute insult, growth factors such as the epidermal growth factor (EGF), insulin-like growth factor (IGF), and fibroblast growth factor (FGF) can promote renal repair and renal function restoration in animal models (13).…”

“…These broad signaling factors are capable of promoting cell proliferation, angiogenesis, and wound healing ( 30 ). Paracrine or extracellular vesicle-delivered growth factors, such as hepatocyte growth factor (HGF) or VEGF, represent additional mechanisms by which MSCs exert therapeutic effects on renal injury ( 13 ).…”

“…Release of proangiogenesis growth factors such as VEGF, and proliferative growth factors (IGF, EGF) that promote cellular repair and promote cell regeneration ( 13 , 51 ).…”

TAB1 regulates glycolysis and activation of macrophages in diabetic nephropathy

“…Transforming growth factor β-activated kinase 1-binding protein 1 (TAB1) is a specific protein that interacts with transforming growth factor β-activated kinase 1 (TAK1). TAB1/TAK1 can activate nuclear factor κB (NF-κB) in high glucose (HG)-induced BMMs, regulating macrophage activation [8][9][10][11][12]. Studies suggest that activation of the NF-κB signaling pathway upregulates HIF-1α activity and enhances glycolytic metabolism in an autonomous fashion, HIF-1α may be considered as a novel therapeutic target for DN [13][14][15][16].…”