Kidney Diseases: HMGB1 as a Potential Therapeutic Strategy

Among the promising avenues of research in kidney-related diseases is the role of High Mobility Group Box 1 (HMGB1). Has been underscored HMGB1’s potential as a strategic target for therapeutic intervention in chronic kidney diseases (CKD), spotlighting its multifaceted roles in chronic inflammation, renal fibrosis, and the exacerbation of nephrotoxicity induced by cancer treatments such as cisplatin.
Recent studies delineates the STAT1/HMGB1/NF-κB signaling pathway’s crucial role in kidney damage following repeated low-dose cisplatin (RLDC) exposure. Blockade of HMGB1, using neutralizing antibodies or pharmacological agents significantly mitigated NF-κB activation and its consequent pro-inflammatory cytokine production. This not only reduces renal tubular injury and fibrosis but also substantially improves renal function post-RLDC treatment

Additionally, a comprehensive review on targeting HMGB1 in CKD highlighted its multifaceted role in the disease’s progression. HMGB1 is involved in several key pathological processes, including renal inflammation, fibrosis, and the AKI-to-CKD transition. Inisghts from studies on hemorrhagic shock and SARS-CoV-2-induced renal fibrosis reveal HMGB1’s modulation by factors such as SIRT1, influencing its release and subsequent pro-inflammatory actions, and its role in the autophagic degradation of fibrogenic mediators like TGF-β1 under therapeutic interventions.
These studies mark a significant stride towards harnessing HMGB1 as a therapeutic target in kidney diseases, fuelling the pursuit of HMGB1-centric therapies, in our quest to face such diseases more effectively.

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