Role of Trichocytic Keratins in Anti-Neuroinflammatory Effects After Spinal Cord Injury

Wenjie Zhong; Dongjie Shi; Junjie ZhouYaying YangBochu WangXiaochuan SunQian ShuWenfeng LiYongzhi XiaLei AoKangLin XiongShilei HaoHaijian Xia

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Role of Trichocytic Keratins in Anti-Neuroinflammatory Effects After Spinal Cord Injury

机译：Role of Trichocytic Keratins in Anti-Neuroinflammatory Effects After Spinal Cord Injury

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Shifting microglia/macrophages to M2 anti-inflammatory phenotype isconsidered a pivotal therapeutic target for spinal cord injury (SCI). Keratinextracted from human hair exhibits anti-inflammatory properties. However,the differences among the 17 types of human hair keratins and their mechanismsof anti-inflammation remain poorly understood. In this study, theanti-inflammatory activity of 17 human hair keratins using a recombinantsynthesis approach is explored. Distinct activities of microglia/macrophagephenotype modulation of 17 keratins are found through qRT-PCR analysis,and recombinant keratin 33A (RK33A) and RK35 display superior anti-inflammatoryefficiency compared to other keratins. Immunofluorescence and flowcytometry reveals a significant effect of RK33A on the regulation of microglia/macrophages into an anti-inflammatory M2 phenotype. Subsequently,recombinant keratin 33A nanofiber (RKNF33A) is fabricated to evaluate itsin vivo anti-inflammatory and nerve regeneration properties using the rat T9spinal cord lateral hemisection model. The optimized keratin-based nanofibershows outstanding performance in enhancing M2 polarization, reducing glialscarring, promoting nerve regeneration, and improving locomotor functionrecovery in SCI rats. Moreover, it is preliminarily found that RK33A regulatesM2 microglia/macrophage polarization by upregulating the PI3K/AKT/mTORsignaling pathway. Together, this study reveals that trichocytic keratins exhibitdistinct anti-inflammatory properties, providing a prospective treatment forSCI by modulating microglia/macrophage polarization.

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《Advanced functional materials》 |2023年第23期|2212870.1-2212870.13|共13页
作者
Wenjie Zhong; Dongjie Shi; Junjie ZhouYaying YangBochu WangXiaochuan SunQian ShuWenfeng LiYongzhi XiaLei AoKangLin XiongShilei HaoHaijian Xia;
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Department of NeurosurgeryThe First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016, China;

Department of PathologyMolecular Medicine and Tumor CenterChongqing Medical UniversityChongqing 400016, China;

Key Laboratory of Biorheological Science and TechnologyMinistry of Education, College of BioengineeringChongqing UniversityChongqing 400030, China;

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正文语种英语
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microglia/macrophage polarization; neuroregeneration; recombinant trichocytic keratins; spinal cord injury;

Role of Trichocytic Keratins in Anti-Neuroinflammatory Effects After Spinal Cord Injury

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