Role of necroptosis in infection‐related, immune‐mediated, and autoimmune skin diseases

Abstract

As the body's largest organ, the skin mainly acts as a physical barrier.It is the first line of defense against infection and injury, protecting the body from potential attacks by exotic organisms or toxic substances.At the same time, it is essential for the regulation of temperature and humidity, substance metabolism, and so forth. The skin is also an interface with the external environment, and its sensory ability helps individuals to interact amicably with the environment. Because it is directly exposed to the environment, it is frequently damaged. For this reason, skin diseases are very common. Although most skin diseases are not life-threatening, they may affect the appearance and make those with skin conditions vulnerable to harmful psychological effects. Therefore, research on the pathogenesis of skin diseases has traditionally been the direction of researchers' efforts.Cell death mechanisms can be traditionally classified into two types: programmed cell death (PCD) mechanisms and necrotic cell death. For many years, apoptosis was thought to be the only form of PCD. Until in the last decade, evidence suggested that additional forms of PCD exist, such as necroptosis (programmed necrosis).Necroptosis is a genetically controlled process of cell death and shares common morphological features with multiple PCD, such as increased cellular volume, organelle swelling, and plasma membrane destruction. However, they are activated by different triggers and are executed by different signaling pathways. Apoptosis does not cause an immune response because no cellular material is discharged into the interstitial space and phagocytes do not release inflammatory cytokines. Unlike apoptosis, necroptosis can elicit a strong adaptive immune response. Necroptosis has become an important pathological process of various diseases. At the same time, it is considered to be the mechanism of inhibiting tumor progression in tumor biology.Many excellent studies have explored the signal transduction cascade, pathophysiological correlation, and clinical disease models, such as neurodegeneration, 1 cancer, 2 virus infection, 3 cardiovascular disease, 4 and therapeutic interventions involving necroptosis. In recent years, an

Comprehensive Analysis of Necroptosis-Related Long Noncoding RNA Immune Infiltration and Prediction of Prognosis in Patients With Colon Cancer

“…RNA sequencing (RNA-seq) data and clinical features were obtained from the TCGA database ( https://portal.gdc.cancer.gov/repository ) ( Liu et al, 2018 ) on 22 September 2021, including 473 tumor datasets and 41 normal datasets. Data for 31 necroptosis-related genes were obtained from the GSEA website ( https://www.gsea-msigdb.org/gsea ) and prior reviews ( Hanson, 2016 ; Chen et al, 2019 ; Molnár et al, 2019 ; Zhu et al, 2019 ; Liu et al, 2021b ). Before comparison, the expression data were standardized to fragment per kilobase million (FPKM) values ( Conesa et al, 2016 ).…”

A Necroptosis-Related lncRNA-Based Signature to Predict Prognosis and Probe Molecular Characteristics of Stomach Adenocarcinoma

“…Subsequently, all patient information was randomly allocated into the training and the testing sets via the “caret” package in R (version 4.1.0, https://www.r-project.org/ ). A total of 39 necroptosis-related genes was acquired by searching published studies ( Hanson, 2016 ; Chen et al, 2019 ; Molnár et al, 2019 ; Zhu et al, 2019 ; Liu et al, 2021 ). In addition, the mutation data of STAD samples were downloaded in MAF format from the TCGA database.…”

“…org/). A total of 39 necroptosis-related genes was acquired by searching published studies (Hanson, 2016;Chen et al, 2019;Molnár et al, 2019;Zhu et al, 2019;Liu et al, 2021). In addition, the mutation data of STAD samples were downloaded in MAF format from the TCGA database.…”

Burn Injury: Mechanisms of Keratinocyte Cell Death

“…Reddy et al [52] reported a pathway of regulated cell necrosis (necroptosis) in burn injury that involved death-receptor-mediated activation of RIPK3 (receptor-interacting serine/threonine-protein kinase 3). RIP kinases (RIPK1/RIPK3, necrosome) are critically involved in this caspase-independent pathway of regulated necrosis, which can be induced through a death receptor-dependent upstream pathway, leading to cell lysis and the release of immunogens [53,54]. In contrast to other diseases, such as cerebrovascular disease [55] and ischemia/reperfusion injury in skin flaps [56], blocking this pathway did not reduce cell death in thermally injured skin, which calls into question the importance of necroptosis in burns.…”