AUTHOR=Li Chenglong , Fei Chengshuo , Le Shiyong , Lai Zhongming , Yan Bo , Wang Liang , Zhang Zhongmin 

TITLE=Identification and validation of ferroptosis-related biomarkers in intervertebral disc degeneration

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=12

YEAR=2024

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2024.1416345

DOI=10.3389/fcell.2024.1416345

ISSN=2296-634X

ABSTRACT=<sec><title>Introduction</title><p>Ferroptosis plays a significant role in intervertebral disc degeneration (IDD). Understanding the key genes regulating ferroptosis in IDD could reveal fundamental mechanisms of the disease, potentially leading to new diagnostic and therapeutic targets.</p></sec><sec><title>Methods</title><p>Public datasets (GSE23130 and GSE70362) and the FerrDb database were analyzed to identify ferroptosis-related genes (DE-FRGs) involved in IDD. Single-cell RNA sequencing data (GSE199866) was used to validate the specific roles and expression patterns of these genes. Immunohistochemistry and Western blot analyses were subsequently conducted in both clinical samples and mouse models to assess protein expression levels across different tissues.</p></sec><sec><title>Results</title><p>The analysis identified seven DE-FRGs, including <italic>MT1G</italic>, <italic>CA9</italic>, <italic>AKR1C1</italic>, <italic>AKR1C2</italic>, <italic>DUSP1</italic>, <italic>CIRBP</italic>, and <italic>KLHL24</italic>, with their expression patterns confirmed by single-cell RNA sequencing. Immunohistochemistry and Western blot analysis further revealed that <italic>MT1G</italic>, <italic>CA9</italic>, <italic>AKR1C1</italic>, <italic>AKR1C2</italic>, <italic>DUSP1</italic>, and <italic>KLHL24</italic> exhibited differential expression during the progression of IDD. Additionally, the study highlighted the potential immune-modulatory functions of these genes within the IDD microenvironment.</p></sec><sec><title>Discussion</title><p>Our study elucidates the critical role of ferroptosis in IDD and identifies specific genes, such as <italic>MT1G</italic> and <italic>CA9</italic>, as potential targets for diagnosis and therapy. These findings offer new insights into the molecular mechanisms underlying IDD and present promising avenues for future research and clinical applications.</p></sec>