LDL receptor-related protein 1 (LRP1), a novel target for opening the blood-labyrinth barrier (BLB)

Su, Xi; Wang, Zihao; Ren, Wei; Chen, Long; Xu, Cong; Li, Menghua; Fan, Shiyong; Xu, Yuru; Chen, Mengbing; Zheng, Fanjun; Zhang, Wenyuan; Zhou, Xinbo; Zhang, Yue; Qiu, Shuo; Wu, Liyuan; Zhou, Peng; Lv, Xianshu; Cui, Tianyu; Qiao, Yuehua; Zhao, Hui; Guo, Weiwei; Chen, Wei; Li, Song; Zhong, Wu; Lin, Jian; Yang, Shiming

doi:10.1038/s41392-022-00995-z

Cited by 15 publications

(11 citation statements)

References 27 publications

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“…More importantly, low-density lipoprotein receptor-related protein 1 (LRP1) was found to localize in the blood-labyrinth barrier and inner hair cells according to new research ( Shi et al, 2022 ). As an important receptor for LTF ( Li and Guo, 2021 ), LRP1 has the potential to break the restriction of BLB and deliver LTF to the inner ear.…”

Section: Discussionmentioning

confidence: 99%

Identification and experimental validation of ferroptosis-related gene lactotransferrin in age-related hearing loss

Zeng,

Gu,

Chen

et al. 2024

Front. Aging Neurosci.

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ObjectiveTo reveal the relationship between ARHL and ferroptosis and screen ferroptosis-related genes (FRGs) in ARHL.MethodsBioinformatics were used to analyze the hub genes and molecular mechanism of ferroptosis in the aging cochleae. Senescence β-galactosidase staining, iron content detection, and micro malondialdehyde (MDA) assay kits were used to measure β-galactosidase activity, and expression of Fe2+ and MDA, respectively. Fluorescence microscope was used for immunofluorescence assay of hub genes. Western blot was used to verify the expression of hub genes in HEI-OC1 cells, cochlear explants, and cochleae of C57BL/6J mice. Data were expressed as mean ± SD of at least three independent experiments.ResultsThe analysis of bioinformatics confirmed that lactotransferrin (LTF) is the hub gene and CEBPA-miR-130b-LTF network is the molecular mechanism for cochlear ferroptosis. Compared with the control group, the experiments proved that the indicators of ferroptosis, including Fe2+, MDA, and LTF were differentially expressed in aging HEI-OC1 cells, aging cochlear explants, and aging cochleae.ConclusionThese results demonstrate that ferroptosis plays an important role in ARHL, and LTF is a potential therapeutic target for ARHL via regulating cochlear ferroptosis.

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Section: Discussionmentioning

confidence: 99%

Identification and experimental validation of ferroptosis-related gene lactotransferrin in age-related hearing loss

Zeng,

Gu,

Chen

et al. 2024

Front. Aging Neurosci.

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“…Surprisingly, we found that apoVs enriched in cochlea especially stria vascularis, spiral ganglion cells and hair cells after systematic administration. Besides their smaller diameter, the mechanism behind may relate to a new-found target for blood-labyrinth barrier, LRP1 (low-density lipoprotein receptor-related protein 1) [ 52 ], which was also identified in apoVs according to our proteomics analysis (Additional file 1 : Table S1). What’s more, apoVs showed more advantages in inner ear delivery.…”

Section: Discussionmentioning

confidence: 99%

Apoptotic vesicles resist oxidative damage in noise-induced hearing loss through activation of FOXO3a-SOD2 pathway

et al. 2023

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Background Mesenchymal stem cell (MSC) transplantation is a promising therapeutic approach for noise-induced hearing loss (NIHL). As the indispensable role of apoptosis in MSC transplantation was raised, the benefits of MSC-derived apoptotic vesicles (apoVs) in several disease models have been proved. However, whether apoVs benefit in NIHL have not been studied yet. Methods Female CBA/J mice and HEI-OC1 cells were used in this study. Flow cytometry, nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) were used to characterize apoVs. Proteomic analysis was used to identify function proteins in apoVs. Immunofluorescence was used to reveal distribution pattern. Auditory brainstem response (ABR) test was used to measure the effect of apoVs treatment. DCFH-DA staining and MitoSOX staining were used to indicate oxidative damage. Western-blot and qRT-PCR were used to study the signaling pathways. Results We found that apoVs can be endocytosed by hair cells through systemic administration. Importantly, apoVs administration effectively attenuated NIHL and reduced hair cell loss by resisting oxidative damage in vivo. Further, apoVs application activated forkhead box o3 (FOXO3a)—mitochondrial superoxide dismutase 2(SOD2) pathway, which may relate to signal transduction and activators of transcription 3 (STAT3) in apoVs. Conclusions These findings uncovered the role of apoVs in preventing NIHL and resisting oxidative damage, indicating that apoVs is a promising way for inner ear delivery and a prospective cell-free therapy for NIHL.

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“…Although the idea of utilizing the innate biological transport mechanisms to cross the BLB for drug delivery is still in its infancy, it could be facilitated in the near future. One recent study found that the low-density lipoprotein receptor-related protein 1 (LRP-1) on the BLB can be a potential target for shuttling therapeutics across this barrier 127 , and its therapeutic value in facilitating the NIHL treatment has not been testified yet. Another approach to be explored in this field is cell-mediated drug delivery.…”

Section: Translational Dilemma From Animals To Humanmentioning

confidence: 99%

Intrinsic mechanism and pharmacologic treatments of noise-induced hearing loss

Xu¹,

Gu²,

Wang³

et al. 2023

Theranostics

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Noise accounts for one-third of hearing loss worldwide. Regretfully, noise-induced hearing loss (NIHL) is deemed to be irreversible due to the elusive pathogenic mechanisms that have not been fully elucidated. The complex interaction between genetic and environmental factors, which influences numerous downstream molecular and cellular events, contributes to the NIHL. In clinical settings, there are no effective therapeutic drugs other than steroids, which are the only treatment option for patients with NIHL. Therefore, the need for treatment of NIHL that is currently unmet, along with recent progress in our understanding of the underlying regulatory mechanisms, has led to a lot of new literatures focusing on this therapeutic field. The emergence of novel technologies that modify local drug delivery to the inner ear has led to the development of promising therapeutic approaches, which are currently under clinical investigation. In this comprehensive review, we focus on outlining and analyzing the basics and potential therapeutics of NIHL, as well as the application of biomaterials and nanomedicines in inner ear drug delivery. The objective of this review is to provide an incentive for NIHL's fundamental research and future clinical translation.

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LDL receptor-related protein 1 (LRP1), a novel target for opening the blood-labyrinth barrier (BLB)

Cited by 15 publications

References 27 publications

Identification and experimental validation of ferroptosis-related gene lactotransferrin in age-related hearing loss

Identification and experimental validation of ferroptosis-related gene lactotransferrin in age-related hearing loss

Apoptotic vesicles resist oxidative damage in noise-induced hearing loss through activation of FOXO3a-SOD2 pathway

Intrinsic mechanism and pharmacologic treatments of noise-induced hearing loss

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