ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cell Growth and Division
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1625058
IL-6 signaling is required for the development and regeneration of ear cartilage in microtia IL-6 signaling in microtia
Provisionally accepted
- Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng, China
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Congenital microtia is a birth defect characterized by auricular underdevelopment, with unclear pathogenesis and unidentified pathogenic genes. Differential expression analysis, weighted coexpression network analysis (WGCNA), protein-protein interaction (PPI) networks and support vector machinerecursive feature elimination (SVM-RFE) identified the key biomolecules in microtia.Single-cell and intercellular communication analysis were used to decipher the key intercellular signaling pathway.We extracted primary cells and conducted Immunoprecipitation mass spectrometry (IP-MS), coImmunoprecipitation (Co-IP) and RNA-sequencing (RNA-seq) to confirmed the mechanism. The intercellular communication network was confirmed through the cell co-culture system. Organoid and animal models further validated the role of key biomolecules.We found that IL-6 may be the key biomolecule in microtia. Normal ear cartilage tissue is mainly composed of chondrocytes, but microtia auricular ear tissue contained chondrocytes and stem cells. IL-6 signaling pathway is the main intercellular communication pathways in microtia. We extracted primary chondrocytes and stem cells, and proved that IL-6 promotes the growth and migration of primary cells. The binding of IL-6 and IL-6R and Glycoprotein 130 (GP130) and the activation of their downstream were confirmed. Furthermore, IL-6 signaling pathway was proved to involve in the intercellular communication of microtia. Cartilage microspheres demonstrated the role of IL-6 in regeneration of ear cartilage. The preventive intervention of adeno-associated virus (AAV) on pregnant mice confirmed the role of IL-6 in vivo.IL-6 signaling is the key biomolecule in the development and regeneration of auricular cartilage in microtia. IL-6 is a potential biomarker and preventive and therapeutic target for microtia patients.
Keywords: microtia, IL-6, intercellular communication, cartilage microspheres, development and regeneration of auricular cartilage
Received: 08 May 2025; Accepted: 17 Jul 2025.
Copyright: © 2025 Luan, fan, jiang, jiang, yang and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Leren He, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng, China
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