Yihao Wang | Search PubMed

PubMed2026

Mitochondrial dysfunction in the pathogenesis of intervertebral disc herniation: a mitochondrial related genome-wide Mendelian randomization analysis.

BACKGROUND: As a degenerative disease, the pathophysiology of intervertebral disc herniation (IDH) closely related to mitochondrial dysfunction. However, the specific molecular mechanisms involved have yet to be precisely established. METHODS: Here, we employed a two-sample, two-step Mendelian Randomization (MR) approach, along with summary-Data-Based MR, genetic colocalization, full phenomenon association analysis, and GO and KEGG enrichment analysis to investigate the genetical effects of mitochondrial dysfunction on IDH. RESULTS: From the intercross between mitochondrial-related genes and eQTLGen genes, we obtained seven genes (DMPK, EHHADH, SLC25A16, ME3, METTL17, TUFM, NDUFA13) with strong causal association with disc herniation. By SMR and genetic colocalization analysis, we further identify five key genes (EHHADH, METTL17, TUFM, NDUFA13, DMPK) as the direct causal tartgeted genes with no heterogeneity and pleiotropy in the SNPs of the genes. Full phenomenon Mendelian randomization was performed to determine possible side effects of the 5 targeting genes. Finally, we validated the expressions of key genes in the degenerative intervertebral discs tissues by qRT-PCR and double-immunofluorescence examinations, and the results were consistent with the MR analysis. CONCLUSIONS: Our study provided genetic support for the relationship between mitochondrial related genes and IDH, implicating potential therapeutic targets for future development. However, more basic experiments need to be finished to validate the role of key genes in the development of IDH.

Intervertebral Disc Displacement↗

PubMed2025

Plasma Proteomic Profiling Reveals ITGA2B as A Key Regulator of Heart Health in High-altitude Settlers.

Myocardial injury is a common disease in the plateau, especially in the lowlanders who have migrated to the plateau, in which the pathogenesis is not well understood. Here, we established a cohort of lowlanders comprising individuals from both low-altitude and high-altitude areas and conducted plasma proteomic profiling. Proteomic data showed that there was a significant shift in energy metabolism and inflammatory response in individuals with myocardial abnormalities at high altitude. Notably, integrin alpha-Ⅱb (ITGA2B) emerged as a potential key player in this context. Functional studies demonstrated that ITGA2B upregulated the transcription and secretion of interleukin-6 (IL-6) through the integrin-linked kinase (ILK)/nuclear factor-κB (NF-κB) signaling axis under hypoxic conditions. Moreover, ITGA2B disrupted mitochondrial structure and function, increased glycolytic capacity, and aggravated energy reprogramming from oxidative phosphorylation to glycolysis. Leveraging the therapeutic potential of traditional Chinese medicine in cardiac diseases, we discovered that tanshinone ⅡA (TanⅡA) effectively alleviated the myocardial injury caused by the abnormally elevated expression of ITGA2B and hypobaric hypoxia exposure in mice, thus providing a novel candidate therapeutic strategy for the prevention and treatment of high-altitude myocardial injury.

Animals↗