Current Protein and Peptide Science - Volume 20, Issue 8, 2019

Acute kidney injury (AKI) is a systemic disease characterized by acute loss of renal function and accumulation of end products of nitrogen metabolism. Ischemic AKI is the most common cause of AKI, and inflammatory responses are inevitablely involved in ischemic AKI. In the process of ischemic AKI, multiple factors are involved in activating and recruitment of immune cell to the injured kidney. These factors include DAMPs and HIFs released from the injured kidney, increased expression of adhesion molecules, the production of chemokines and cytokines, activation of complement system and TLRs as well as the permeability dysfunction of the renal vascular endothelium. Immune cells of both the innate and adaptive immune systems, such as neutrophils, dendritic cells, macrophages and lymphocytes contribute to the pathogenesis of renal injury after ischemia reperfusion injury (IRI), with some of their subpopulations also participating in the repair process. Numerous studies of immune cells involved in the pathogenesis of AKI have enhanced the understanding of their possible mechanisms in AKI which might become the potential targets for the treatment of ischemic AKI. This review describes the function of the immune cells in the pathogenesis and repair of ischemic AKI and emphasizes the treatment of ischemic AKI potentially targeting them.

Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) that is a global health concern associated with high morbidity and mortality. So far, no specific interventions limit injury or improve recovery and survival. Transient receptor potential melastatin 7 (TRPM7), a bifunctional membrane protein, plays key roles in inflammation and cell death. However, the precise role and underlying mechanism of TRPM7 in IR-induced AKI have not been well defined. Herein, we reviewed the structure and function of TRPM7 as a non-selective ion channel, but Ca2+ and Mg2+-conducting, that mediated the elevation of cytosolic Ca2+ and Mg2+. We then comprehensively reviewed the mechanism of TRPM7 involved in the pathophysiology of renal IRI, including inflammatory response, apoptosis and necroptosis, renal microvasculature, as well as maladaptive fibrogenesis leading to chronic kidney disease (CKD). Our previous study has shown that the dynamic change and underlying mechanism of TRPM7 involving in inflammation and apoptosis in in vitro hypoxia/reoxygenation and in vivo renal IRI models. The association between TRPM7, inflammatory response and apoptosis, as well as related caspase-3, HMGB1 and Bax/Bcl-2 ratio, was also discussed. Disclosing the involvement of TRPM7 in renal IRI might provide new mechanistic insights for a potential biomarker as diagnostic and therapeutic target of AKI.

Intracranial aneurysms (IA) are a huge threat to human health, with a global incidence rate of 0.65–8.4%. Although the microsurgical and interventional techniques have made profound progression in treating IA, the relatively high rate of complications and recurrence are still not satisfactory. Thus, there is a need to elucidate its molecular mechanism. Numerous studies have identified the close relationship between hemodynamic-induced inflammation and development of IA. Indeed, the dysfunction of endothelial cells, smooth muscle cells, macrophages and lymphocytes, as well as their secreted cytokines, collectively contribute to the formation, growth and rupture of IA. Furthermore, the immune system has also been identified to participate in the development of IA. This review will explore the mechanisms of various inflammatory cells and significant cytokines, providing a new perspective in the clinical treatment of IA.

Sepsis, which is a highly heterogeneous syndrome, can result in death as a consequence of a systemic inflammatory response syndrome. The activation and regulation of the immune system play a key role in the initiation, development and prognosis of sepsis. Due to the different periods of sepsis when the objects investigated were incorporated, clinical trials often exhibit negative or even contrary results. Thus, in this review we aim to sort out the current knowledge in how immune cells play a role during sepsis.

Autophagy entails the removal of dysfunctional components to maintain cellular homeostasis. Over the years, studies of autophagy demonstrated its complex physiological and pathological roles in the liver. Apart from regulation of normal metabolic functions such as glycogenolysis, glycogenesis, and β-oxidation, autophagy also contributes to the modulation of various liver diseases. In this review, we provide a concise overview of the role of autophagy in regulating hepatic metabolism in healthy conditions and various chronic liver diseases. A well-rounded understanding of the role of autophagy may provide insight for future medical advancements in the field of hepatology.

Siglecs are mammalian sialic acid (Sia) recognizing immuno-globulin-like receptors expressed across the major leukocyte lineages, and function to recognize ubiquitous Sia epitopes on the cell surface. Many Siglecs are inhibitory receptors expressed on innate immune cells, they also have a role in maintaining B cell tolerance as well as modulating the activation of conventional and plasmocytic dendritic cells. Through these and other roles they contribute directly and indirectly to the regulation of T cell function. Siglecs have been identified to play key roles in several forms of blood cancers, autoimmune and infection deceases. So far as we know, there’s no Siglecs related research works on solid organ transplantation. In this review, we describe our understanding of the potential roles of Siglecs in the regulation of immune cell function, which may be crosslinked to allo-rejection and ischemia-reperfusion injury.

Inflammation is the first response occurring after damage or infection, which is a defensive process for the body. It is well known that excessive inflammation can lead to further diseases such as fibrosis. But a regenerative inflammatory response can accelerate the process of repairing injury, in which a variety of cytokines, immune cells, and stem cells are involved. The Wnt signaling pathway was originally known in the field of development. Recently, its role in regenerative inflammation has gradually been established. Wnt signaling can regulate cell proliferation and differentiation through regulating participants of regenerative inflammation. Canonical and noncanonical Wnt signaling pathways are coordinated to maintain homeostasis. Based on the process of regenerative inflammation and recent research in this field, this paper reviews how the Wnt signaling pathway interact with other cells and pathways.

During inflammation, chemokines play a central role by mediating the activation of inflammatory cascade responses in tissue injury. Among more than 200 chemokines, CX3CL1 is a special chemotactic factor existing in both membrane-bound and soluble forms. Its only receptor, CX3CR1, is a member of the G protein-coupled receptor superfamily. The CX3CL1/CX3CR1 axis can affect many inflammatory processes by communicating with different inflammatory signaling pathways, such as JAK-STAT, Toll-like receptor, MAPK, AKT, NF-ΚB, Wnt/β-catenin, as well as others. These inflammatory networks are involved in much pathology. Determining the crosstalk between the CX3CL1/CX3CR1 axis and these inflammatory signaling pathways could contribute to solving problems in tissue injury, and the CX3CL1/CX3CR1 axis may be a better therapeutic target than inflammatory signaling pathways for preventing tissue injury due to the complexity of inflammatory signaling networks.