siRNA therapy has great potential in humans, and its applications have been significantly improved. The kidney is a comparatively easy target organ of siRNA therapy due to its unique structural and functional characteristics. Here, we reviewed recent achievements in the design, delivery, and utilization of RNAi with a focus on kidney diseases, in particular acute kidney injury. In addition, the perspectives and challenges of siRNA therapy such as increasing its serum stability and immune tolerance, targeting single/double/multiple genes, cell/allele-specific delivery, time-controlled silencing, and siRNA-modified stem cell therapy were also discussed. Finally, selecting target genes and therapeutic time windows were addressed.
Part of the book: RNA Interference
Erythropoietin (EPO), recognized as a tissue protective agent, can trigger anti-inflammatory and anti-apoptotic processes to delimit injury and promote repair by the binding tissue-protective receptor. However, only at a high dosage can EPO exert tissue protective effects, which simultaneously elicits some severe erythropoiesis-related side effects. Thus, the structural modification of EPO for the prevention of side effects is undoubtedly required. This chapter reviewed the development from EPO to its peptide derivatives with tissue protective efficacy. We also discussed are the therapeutic effects and limitations of each peptide, signaling pathways involved and the benefits for translation.
Part of the book: Polypeptide
Acute kidney injury (AKI) is a prevailing health threat around the world with high mortalities and heavy economic burdens. In the past, apoptosis was recognized as the main contributor to the pathogenesis of AKI. However, recent evidence has suggested that regulated necrosis also plays an important role in the pathologic process of various types of renal damages, improving our limited understanding of the complex mechanisms underlying AKI. Regulated necrosis is a newly identified type of “programed cell death” with morphologic features of necrosis, which includes necroptosis, ferroptosis, parthanatos, pyroptosis, etc. In this chapter, we summarized the molecular pathways of both apoptosis and regulated necrosis, and reviewed the potential roles and corresponding mechanisms of various cell deaths in AKI based on recent advances. We also discussed the therapeutic potentials and clinical implications based on manipulating regulated cell death. Taken together, the progress in this field lays the ground for better prevention and management of AKI in the future.
Part of the book: Current Understanding of Apoptosis