SEM1 Downregulates HSPA8 to Suppress TLR4/MyD88/NF-κB Signaling and Alleviate Myocardial I/R Injury.
J, L., J, K., Z, G., D, T., Y, H., X, T., & X, C. (2026). SEM1 Downregulates HSPA8 to Suppress TLR4/MyD88/NF-κB Signaling and Alleviate Myocardial I/R Injury.. International journal of molecular sciences. https://doi.org/10.3390/ijms27156711
J L, J K, Z G, D T, Y H, X T, et al. SEM1 Downregulates HSPA8 to Suppress TLR4/MyD88/NF-κB Signaling and Alleviate Myocardial I/R Injury.. International journal of molecular sciences. 2026; doi: 10.3390/ijms27156711
J L, J K, Z G, et al. SEM1 Downregulates HSPA8 to Suppress TLR4/MyD88/NF-κB Signaling and Alleviate Myocardial I/R Injury.[J]. International journal of molecular sciences. 2026. DOI: 10.3390/ijms27156711.
@article{j2026,
author = {Liu J and Kang J and Guan Z and Tian D and Huang Y and Tang X and Chen X},
title = {SEM1 Downregulates HSPA8 to Suppress TLR4/MyD88/NF-κB Signaling and Alleviate Myocardial I/R Injury.},
journal = {International journal of molecular sciences},
year = {2026},
doi = {10.3390/ijms27156711},
note = {PMID: 42589368},
}
TY - JOUR AU - Liu J AU - Kang J AU - Guan Z AU - Tian D AU - Huang Y AU - Tang X AU - Chen X TI - SEM1 Downregulates HSPA8 to Suppress TLR4/MyD88/NF-κB Signaling and Alleviate Myocardial I/R Injury. T2 - International journal of molecular sciences PY - 2026 DO - 10.3390/ijms27156711 AN - PMID:42589368 ER -
Inflammation plays a pivotal role in the pathogenesis of myocardial ischemia/reperfusion (I/R) injury, highlighting inflammation suppression as a critical therapeutic strategy. The inflammatory response is largely mediated through Toll-like receptor 4 (TLR4), a transmembrane signal receptor whose expression is upregulated by Heat Shock Protein Family A Member 8 (HSPA8). Here, we investigated whether SEM1, a subunit of the 26S proteasome, interacts with HSPA8 and attenuates TLR4-mediated inflammation. Our results demonstrate that SEM1 expression is downregulated following myocardial I/R. Overexpression of SEM1 alleviated cardiac injury and dysfunction, inhibited myocardial inflammation, and downregulated HSPA8 expression in the I/R-injured heart. Co-IP assays confirmed a strong physical interaction between SEM1 and HSPA8, while the precise molecular mechanism responsible for SEM1-induced downregulation of HSPA8 remains to be fully elucidated. Mechanistically, SEM1 suppressed the activation of the TLR4/MyD88/NF-κB signaling pathway. Collectively, these findings identify SEM1 as a novel regulator that protects against myocardial I/R injury via its association with HSPA8 and inhibition of the TLR4-mediated inflammatory cascade, offering a promising therapeutic target for this condition.