LRP4 is required for the olfactory association task in the piriform cortex

Yan, Min; Xiong, Mingtao; Wu, Yongqiang; Dong, Lin; Chen, Peng; Jiang, Chen; Liu, Ziyang; Zhang, Hang; Ren, Dongyan; Fei, Erkang; Lai, Xiaojing; Zou, Suqi; Wang, Shunqi

doi:10.1186/s13578-022-00792-9

Cited by 8 publications

(6 citation statements)

References 51 publications

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“…However, surprisingly, we have found that the protective effect exerted by digoxin seems to be unrelated to the inhibition of Na + /K + -ATPase ( Supplementary Figure 1A ). Low-density lipoprotein receptor-related protein 4 (LRP4) is a transmembrane protein involved in various cellular processes, including cell adhesion, migration, and signal transduction ( 29 , 30 ). Recent studies have indicated that LRP4 is a novel target involved in digoxin-mediated regulation of cartilage metabolism ( 22 ).…”

Section: Resultsmentioning

confidence: 99%

Digoxin protects against intervertebral disc degeneration via TNF/NF-κB and LRP4 signaling

Meng,

Liu,

Liu

et al. 2023

Front. Immunol.

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BackgroundIntervertebral disc degeneration (IVDD) is a leading cause of low back pain (LBP). The pathological process of IVDD is associated with inflammatory reactions and extracellular matrix (ECM) disorders. Digoxin is widely used for treating heart failure, and it has been reported to have anti-inflammatory effects.ObjectiveThis study is to investigate the role of digoxin in the pathogenesis of intervertebral disc degeneration as well as the involved molecular mechanism, particularly the potential target protein.MethodsWe exploited a rat needle model to investigate digoxin’s role in intervertebral disc degeneration in vivo. Safranin O staining was used to measure cartilaginous tissue in the intervertebral disc. The morphological changes of intervertebral discs in animal models were determined by Hematoxylin-Eosin (H&E) staining and the pathological score. Primary nucleus pulposus cells (NP cells) from intervertebral discs of patients and murine were used in the present study. Western-Blotting assay, Real-time PCR assay, immunofluorescence staining, and immunochemistry were used to detect the role of digoxin in anti-TNF-α-induced inflammatory effects in vitro. Transfection of siRNA was used to regulate low-density lipoprotein receptor-related protein 4 (LRP4) expression in NP cells to investigate the potential protein target of digoxin.ResultsDigoxin protected against intervertebral disc degeneration in rat needle models. Digoxin was found to exert its disc-protective effects through at least three different pathways by a) suppressing TNF-α-induced inflammation, b) attenuating ECM destruction, c) significantly promoting ECM anabolism. Additionally, LRP4 was found to be the downstream molecule of digoxin in NP cells for anti-inflammation and regulation of ECM metabolism. The knockdown of LRP4 downregulated the protective effect of digoxin in NP cells.ConclusionThese findings suggest that digoxin may be a potential therapeutic agent for intervertebral disc degeneration through anti-catabolism and pro-anabolism. Digoxin might also work as an alternative for other inflammation-related diseases.

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Section: Resultsmentioning

confidence: 99%

Digoxin protects against intervertebral disc degeneration via TNF/NF-κB and LRP4 signaling

Meng,

Liu,

Liu

et al. 2023

Front. Immunol.

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“…CHSY1 is indispensable for skeletal development and the promotion of bone length (Wilson et al, 2012). MDK and LEF1 assume vital roles in cartilage development, skeletal growth, and osteoblast differentiation and regeneration (Haffner-Luntzer et al, 2016;Yan et al, 2022). In the context of GO:0042475 (odontogenesis of dentin-containing tooth), the key genes WNT6, LEF1, LRP4, and TP63 play pivotal roles in dental cell differentiation, skeletal development, and osteoblast differentiation (Ahn et al, 2017;Luo et al, 2019;Wei et al, 2020;Gong et al, 2021).…”

Section: Exploring the Regulatory Mechanisms Of High-altitude Adaptiv...mentioning

confidence: 99%

Genetic diversity and runs of homozygosity analysis of Hetian sheep populations revealed by Illumina Ovine SNP50K BeadChip

Han,

Zhou,

Zhang

et al. 2023

Front. Ecol. Evol.

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Hetian sheep have a long history and a wide distribution. They are renowned for their carpet-grade wool, which makes them a valuable genetic resource in China. The survey revealed that Hetian sheep primarily inhabit three distinct ecological environments: mountains (MTS), mountain–grasslands (MGTS), and grasslands (GTS). To understand the evolutionary relationships and germplasm characteristics of Hetian sheep in these diverse environments, we randomly selected 84 healthy adult ewes from each of these ecological regions. We obtained the Illumina Ovine SNP50K BeadChip by extracting DNA from Hetian sheep ear tissue using the phenol-chloroform method. Afterward, we conducted a population genetic structure and genetic diversity analysis of Hetian sheep using the Illumina Ovine SNP50K Beadchip. Principal component analysis (PCA) and neighbor-joining (NJ) phylogenetic analysis indicated that Hetian sheep in three different ecological environments exhibit distinct genetic distances. Admixture analysis indicated that MGTS and GTS share a common ancestral origins. Additionally, the linkage disequilibrium (LD) analysis indicated that M had the highest decay rate, while MG had the lowest decay rate. Furthermore, we identified the overlapping homozygous genomic regions of Hetian sheep in the three ecological environments through runs of homozygosity (ROH) analysis. We subsequently performed gene annotation and enrichment analysis on these overlapping genomic regions. In the MTS environment, we identified 31 candidate genes associated with high-altitude environmental adaptation. These genes are involved in bone cell generation, differentiation, and the maintenance of bone homeostasis (WNT6, WNT10A, and CHSY1); tooth and tongue development (LEF1, TP63, and PRDM16); and hearing and visual functions (RBP4, ATF6, and JAG1). In the GTS environment, we identified 22 candidate genes related to economic traits, including those associated with reproduction (PLA2G4F, ACVR1, and ADCY2) and growth (CAPN3, YAP1, and FGF9). Research indicates that Hetian sheep can be divided at the genomic level into three subtypes: MTS, MGTS, and GTS. This enhances the genetic diversity of Hetian sheep germplasm resources and provides guidance for the conservation of Hetian sheep breeds. Additionally, we have identified genes related to multiparous traits in MGTS and GTS, offering insights for the selection and breeding of multiparous Hetian sheep.

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“…WB was performed as previously described, with minor modifications [35]. In brief, the cells were collected, and the proteins were extracted via RIPA (1.0% NP-40, 150 mm NaCl, 50 mm pH 8.0 Tris, 0.5% Na-deoxycholate, 0.1% SDS), supplemented with 1% PMSF (Phenyl-methane sulfonyl fluoride) and protease inhibitor cocktail (Cat.…”

Section: Western Blotting (Wb)mentioning

confidence: 99%

A Novel Form of Neuregulin 1 Type III Caused by N-Terminal Processing

Wang,

Zhang,

Wang

et al. 2023

Biomolecules

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Nrg1 (Neuregulin 1) type III, a susceptible gene of schizophrenia, exhibits a critical role in the central nervous system and is essential at each stage of Schwann’s cell development. Nrg1 type III comprises double-pass transmembrane domains, with the N-terminal and C-terminal localizing inside the cells. The N-terminal transmembrane helix partially overlaps with the cysteine-rich domain (CRD). In this study, Nrg1 type III constructs with different tags were transformed into cultured cells to verify whether CRD destroyed the transmembrane helix formation. We took advantage of immunofluorescent and immunoprecipitation assays on whole cells and analyzed the N-terminal distribution. Astonishingly, we found that a novel form of Nrg1 type III, about 10% of Nrg1 type III, omitted the N-terminal transmembrane helix, with the N-terminal positioning outside the membrane. The results indicated that the novel single-pass transmembrane status was a minor form of Nrg1 type III caused by N-terminal processing, while the major form was a double-pass transmembrane status.

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LRP4 is required for the olfactory association task in the piriform cortex

Cited by 8 publications

References 51 publications

Digoxin protects against intervertebral disc degeneration via TNF/NF-κB and LRP4 signaling

Digoxin protects against intervertebral disc degeneration via TNF/NF-κB and LRP4 signaling

Genetic diversity and runs of homozygosity analysis of Hetian sheep populations revealed by Illumina Ovine SNP50K BeadChip

A Novel Form of Neuregulin 1 Type III Caused by N-Terminal Processing

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