Cisplatin is widely used in clinical tumor chemotherapy but has severe ototoxic side effects, including tinnitus and hearing damage. This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity. In this study, we used CBA/CaJ mice to establish an ototoxicity model of cisplatin-induced hair cell loss, and our results showed that cisplatin treatment could reduce FOXG1 expression and autophagy levels. Additionally, H3K9me2 levels increased in cochlear hair cells after cisplatin administration. Reduced FOXG1 expression caused decreased microRNA (miRNA) expression and autophagy levels, leading to reactive oxygen species (ROS) accumulation and cochlear hair cell death. Inhibiting miRNA expression decreased the autophagy levels of OC-1 cells and significantly increased cellular ROS levels and the apoptosis ratio . , overexpression of FOXG1 and its target miRNAs could rescue the cisplatin-induced decrease in autophagy, thereby reducing apoptosis. BIX01294 is an inhibitor of G9a, the enzyme in charge of H3K9me2, and can reduce hair cell damage and rescue the hearing loss caused by cisplatin . This study demonstrates that FOXG1-related epigenetics plays a role in cisplatin-induced ototoxicity through the autophagy pathway, providing new ideas and intervention targets for treating ototoxicity.
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http://dx.doi.org/10.3389/fnmol.2023.1064579 | DOI Listing |
Cells
December 2024
Department of Immunology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
The hair follicle is a complex of mesenchymal and epithelial cells acquiring different properties and characteristics responsible for fulfilling its inductive and regenerative role. The epidermal and dermal crosstalk induces morphogenesis and maintains hair follicle cycling properties. The hair follicle is enriched with pluripotent stem cells, where dermal papilla (DP) cells and dermal sheath (DS) cells constitute the dermal compartment and the epithelial stem cells existing in the bulge region exert their regenerative role by mediating the epithelial-mesenchymal interaction (EMI).
View Article and Find Full Text PDFBMJ Open
January 2025
Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Introduction: Cardiovascular diseases (CVDs) present differently in women and men, influenced by host-microbiome interactions. The roles of sex hormones in CVD outcomes and gut microbiome in modifying these effects are poorly understood. The XCVD study examines gut microbiome mediation of sex hormone effects on CVD risk markers by observing transgender participants undergoing gender-affirming hormone therapy (GAHT), with findings expected to extrapolate to cisgender populations.
View Article and Find Full Text PDFeNeuro
January 2025
Hearing Technology @ WAVES, Department of Information Technology, Ghent University, Technologiepark 216, 9052 Zwijnaarde, Belgium
Speech intelligibility declines with age and sensorineural hearing damage (SNHL). However, it remains unclear whether cochlear synaptopathy (CS), a recently discovered form of SNHL, significantly contributes to this issue. CS refers to damaged auditory-nerve synapses that innervate the inner hair cells and there is currently no go-to diagnostic test available.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
aDepartment of Dermatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China. Electronic address:
Tissue engineering utilizing hydrogel scaffolds in combination with exogenous stem cells holds significant potential for promoting wound regeneration. However, the microenvironment provided by existing skin tissue engineering scaffold materials is often inadequate. Herein, we demonstrate an enzyme-crosslinked hyaluronic acid hydrogel to provide a growth microenvironment for exogenous bone marrow mesenchymal stem cells and promote acute wound healing.
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