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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

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BMP10 Knockdown Modulates Endothelial Cell Immunoreactivity by Inhibiting the HIF‐1α Pathway in the Sepsis‐Induced Myocardial Injury

Published:29 November 2024 DOI: 10.1111/jcmm.70232
Huan Guan, Jingyun Fang

Abstract

Sepsis is a life-threatening syndrome triggered by a cascade of dysregulated immune responses. Sepsis-induced myocardial injury (SIMI) substantially impacts the survival time of septic patients. However, the molecular mechanisms underlying the pathology of SIMI remain unclear. Immune-related differentially expressed genes in SIMI were identified through RNA sequencing and bioinformatics analysis. The expression levels of hub genes were detected using reverse transcription quantitative PCR. BMP10 was knocked down in the lipopolysaccharide-induced mouse and cardiac microvascular endothelial cell (CMEC) models, and its functions were assessed by a series of in?vitro and in?vivo assays. Cell adhesion and HIF-1 pathway-associated protein expressions were measured by western blot. Fenbendazole-d3 was used to investigate whether BMP10 influenced SIMI development by modulating the HIF-1 pathway. Six key genes were screened, of which BMP10, HAMP, TRIM5, and MLANA were highly expressed, and PTPRN2 and AVP were lowly expressed. BMP10 knockdown ameliorated histopathological changes and inhibited apoptosis and CMEC immune infiltration in SIMI. BMP10 knockdown reduced inflammatory factor (IL-6, MCP-1, IFN-β, and CCL11) levels and protein expressions of cell adhesion-related molecules (VCAM-1 and ICAM-1). Mechanistically, the HIF-1 pathway agonist, Fenbendazole-d3, significantly reversed the inhibitory effects of BMP10 knockdown on SIMI in?vitro, indicating that BMP10 knockdown impeded the development of SIMI by suppressing the HIF-1α pathway. BMP10 knockdown blocks SIMI progression by inhibiting the HIF-1α pathway, which provides a new potential therapeutic strategy for SIMI treatment.

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Materials
Procduct Name CAS Molecular Formula Supplier Price
Trypsin 9002-07-7 C35H47N7O10 738 suppliers $19.90-$28880.00
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