A Cell-Penetrating Peptide That Blocks Toll-Like Receptor Signaling Protects Kidneys against Ischemia-Reperfusion Injury

Jung, Su Woong; Seo, Jongmin; Park, Seon Hwa; Kim, Yang‐Gyun; Moon, Jae‐Young; Choi, Sangdun; Lee, Sang-Ho

doi:10.3390/ijms22041627

Cited by 4 publications

(2 citation statements)

References 30 publications

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“…To test this idea, cells expressing the reported receptors known to bind to AMP should be analyzed. To the best of our knowledge, there are no CPP-receptor reported interactions, although there are many reports fusing CPP to peptide sequences recognized by receptors [ 72 , 74 ]. This fundamental question about the mechanism of action of CPP is against the notion that CPP are only able to translocate into cells.…”

Section: Cpp Structure–activity Relationshipmentioning

confidence: 99%

Antimicrobial peptides with cell-penetrating activity as prophylactic and treatment drugs

2022

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Health is fundamental for the development of individuals and evolution of species. In that sense, for human societies is relevant to understand how the human body has developed molecular strategies to maintain health. In the present review, we summarize diverse evidence that support the role of peptides in this endeavor. Of particular interest to this review are antimicrobial (AMP) and cell-penetrating peptides (CPP). Different experimental evidence indicates that AMP/CPP are able to regulate autophagy, which in turn regulates the immune system response. AMP also assists in the establishment of the microbiota, which in turn is critical for different behavioral and health aspects of humans. Thus, AMP and CPP are multifunctional peptides that regulate two aspects of our bodies that are fundamental to our health: autophagy and microbiota. While it is now clear the multifunctional nature of these peptides, we are still in the early stages of the development of computational strategies aimed to assist experimentalists in identifying selective multifunctional AMP/CPP to control non-healthy conditions. For instance, both AMP and CPP are computationally characterized as amphipatic and cationic, yet none of these features are relevant to differentiate these peptides from non-AMP or non-CPP. This review aims to highlight current knowledge that may facilitate the development of AMP’s design tools for preventing or treating illness.

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Section: Cpp Structure–activity Relationshipmentioning

confidence: 99%

Antimicrobial peptides with cell-penetrating activity as prophylactic and treatment drugs

2022

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“…Current experimental strategies to prevent or alleviate RIRI can be focused on scavenging ROS, reducing inflammation, or promoting cell survival and regeneration, including cellular therapy, pharmacological treatment, and ischemic preconditioning (9)(10)(11)(12). Despite those methods, there is still a lack of effective treatment in clinical settings (13). Besides, with the expansion of donor pools in recent years, donation after brain death (DBD) and donation after cardiac death (DCD) have been gradually increased.…”

Section: Introductionmentioning

confidence: 99%

Integrated Analysis of Prognostic Genes Associated With Ischemia–Reperfusion Injury in Renal Transplantation

et al. 2021

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BackgroundIschemia–reperfusion injury (IRI) remains an inevitable and major challenge in renal transplantation. The current study aims to obtain deep insights into underlying mechanisms and seek prognostic genes as potential therapeutic targets for renal IRI (RIRI).MethodsAfter systematically screening the Gene Expression Omnibus (GEO) database, we collected gene expression profiles of over 1,000 specimens from 11 independent cohorts. Differentially expressed genes (DEGs) were identified by comparing allograft kidney biopsies taken before and after reperfusion in the discovery cohort and further validated in another two independent transplant cohorts. Then, graft survival analysis and immune cell analysis of DEGs were performed in another independent renal transplant cohort with long-term follow-ups to further screen out prognostic genes. Cell type and time course analyses were performed for investigating the expression pattern of prognostic genes in more dimensions utilizing a mouse RIRI model. Finally, two novel genes firstly identified in RIRI were verified in the mouse model and comprehensively analyzed to investigate potential mechanisms.ResultsTwenty DEGs upregulated in the process of RIRI throughout different donor types (living donors, cardiac and brain death donors) were successfully identified and validated. Among them, upregulation of 10 genes was associated with poor long-term allograft outcomes and exhibited strong correlations with prognostic immune cells, like macrophages. Furthermore, certain genes were found to be only differentially expressed in specific cell types and remained with high expression levels even months after RIRI in the mouse model, which processed the potential to serve as therapeutic targets. Importantly, two newly identified genes in RIRI, Btg2 and Rhob, were successfully confirmed in the mouse model and found to have strong connections with NF-κB signaling.ConclusionsWe successfully identified and validated 10 IRI-associated prognostic genes in renal transplantation across different donor types, and two novel genes with crucial roles in RIRI were recognized for the first time. Our findings offered promising potential therapeutic targets for RIRI in renal transplantation.

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The ability of microRNAs to regulate the immune response in ischemia/reperfusion inflammatory pathways

Artimovič,

Špaková,

Macejková

et al. 2024

Genes Immun

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MicroRNAs play a crucial role in regulating the immune responses induced by ischemia/reperfusion injury. Through their ability to modulate gene expression, microRNAs adjust immune responses by targeting specific genes and signaling pathways. This review focuses on the impact of microRNAs on the inflammatory pathways triggered during ischemia/reperfusion injury and highlights their ability to modulate inflammation, playing a critical role in the pathophysiology of ischemia/reperfusion injury. Dysregulated expression of microRNAs contributes to the pathogenesis of ischemia/reperfusion injury, therefore targeting specific microRNAs offers an opportunity to restore immune homeostasis and improve patient outcomes. Understanding the complex network of immunoregulatory microRNAs could provide novel therapeutic interventions aimed at attenuating excessive inflammation and preserving tissue integrity.

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A Cell-Penetrating Peptide That Blocks Toll-Like Receptor Signaling Protects Kidneys against Ischemia-Reperfusion Injury

Cited by 4 publications

References 30 publications

Antimicrobial peptides with cell-penetrating activity as prophylactic and treatment drugs

Antimicrobial peptides with cell-penetrating activity as prophylactic and treatment drugs

Integrated Analysis of Prognostic Genes Associated With Ischemia–Reperfusion Injury in Renal Transplantation

The ability of microRNAs to regulate the immune response in ischemia/reperfusion inflammatory pathways

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