Apoptosis is a major cause of reduced podocyte numbers, which leads to proteinuria and/or glomerulosclerosis. Emerging evidence has indicated that deSUMOylation, a dynamic post-translational modification that reverses SUMOylation, is involved in the apoptosis of Burkitt’s lymphoma cells and cardiomyocytes; however, the impact of deSUMOylation on podocyte apoptosis remains unexplored. The p53 protein plays a major role in the pathogenesis of podocyte apoptosis, and p53 can be SUMOylated. Therefore, in the present study, we evaluated the effect of p53 deSUMOylation, which is regulated by sentrin/SUMO-specific protease 1 (SENP1), on podocyte apoptosis. Our results showed that SENP1 deficiency significantly increases puromycin aminonucleoside (PAN)-induced podocyte apoptosis. Moreover, SENP1 knockdown results in the accumulation of SUMOylated p53 protein and the increased expression of the p53 target pro-apoptotic genes, BAX, Noxa and PUMA, in podocytes during PAN stimulation. Thus, SENP1 may be essential for preventing podocyte apoptosis, at least partly through regulating the functions of p53 protein via deSUMOylation. The regulation of deSUMOylation may provide a novel strategy for the treatment of glomerular disorders that involve podocyte apoptosis.

Innate immune evasion is a critical aspect of viral infections, as it disrupts the host’s defense mechanisms.The innate immune system, as the primary defense against pathogens, detects pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs). This recognition triggers the production of interferons (IFNs) and pro-inflammatory factors, initiating the antiviral immune response. During evolution, viruses have found many ways to evade innate immune response in order to increase the replication efficiency, transmission ability and to establish persistent infection through co-evolution with hosts. Pigs act as natural hosts for a variety of significant viruses, including both DNA and RNA viruses. These viruses not only jeopardize animal health but also present a potential risk of interspecies transmission. Among these, porcine transmissible gastroenteritis virus (TGEV) stands out as a highly prevalent and severely detrimental enterovirus in the global swine industry. This review aims to comprehensively analyze the interaction between TGEV and host cells, emphasizing the molecular underpinnings of its immune evasion strategies. In addition, we will describe the programmed cell death types induced by TGEV, including autophagy, apoptosis and pyroptosis. Compared with existing reviews, this article not only provides a systematic integration of the multilayered immune evasion mechanisms of TGEV but also, for the first time, offers a comprehensive overview of its interactions with various forms of programmed cell death. This perspective highlights the complex regulatory networks underlying TGEV’s adaptive evolution in the host, thereby enhancing our understanding of the pathogenic mechanisms of porcine coronaviruses and offering novel theoretical foundations for the development of vaccines and antiviral therapeutics.

Ferroptosis, an iron-dependent type of cell death, has attracted significant attention in recent years. Accumulating evidence demonstrates that ferroptosis critically contributes to the pathogenesis of intestinal ischemia/reperfusion (I/R) primarily through triggering excessive lipid peroxidation, disrupting iron homeostasis, and disabling endogenous antioxidant system. Therefore, targeted inhibition of ferroptosis represents a promising therapeutic strategy to alleviate intestinal I/R damage. However, the upstream molecular regulatory networks governing ferroptosis in intestinal I/R, especially miRNA-mediated post-transcriptional regulatory mechanisms, are not fully understood. MiRNA microarray analysis revealed that the expression of miR-381-3p is upregulated following intestinal I/R insult. Bioinformatic prediction combined with dual-luciferase reporter assays confirmed that miR-381-3p directly targets and negatively regulates cAMP response element-binding protein 1 (CREB1), a key transcription factor closely implicated in ferroptosis modulation. Subsequent experiments confirmed that CREB1 specifically binds to the promoter region of peroxiredoxin 6 (PRDX6) to facilitate its transcriptional activation, as quantified by quantitative real-time PCR. Both in vivo intestinal I/R injury mouse models and an in vitro Caco-2 cell hypoxia/reoxygenation (H/R) model were utilized for functional verification. The results revealed that upregulation of the CREB1/PRDX6 axis significantly suppressed the expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), which is a key marker of ferroptosis. Meanwhile, enhanced GPX4 activity and elevated intracellular glutathione (GSH) content were observed, accompanied by reduced intracellular iron overload and alleviated histological and cellular morphological damage. Conversely, inhibition of the CREB1/PRDX6 axis exacerbated ferroptosis, with corresponding adverse changes in these ferroptosis-related indicators. In conclusion, the miR-381-3p/CREB1/PRDX6 signaling axis protects against intestinal I/R by suppressing ferroptosis, providing novel molecular targets and a theoretical basis for the prevention of intestinal I/R injury.