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pmid:37704618

NRP1 transduces mechanical stress inhibition via LATS1/YAP in hypertrophic scars.

Mengzhi Li · Peng Wang · Jingting Li · Fei Zhou · Shixin Huang · Shaohai Qi · Bin Shu

Cell death discovery · 2023 doi:10.1038/s41420-023-01635-3

Paper

complete

Experiment

complete

Data

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partial

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absent

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title
NRP1 transduces mechanical stress inhibition via LATS1/YAP in hypertrophic scars.
doi
10.1038/s41420-023-01635-3
pmid
37704618
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Mengzhi Li
[1]
Peng Wang
[2]
Jingting Li
[3]
Fei Zhou
[4]
Shixin Huang
[5]
Shaohai Qi
[6]
Bin Shu
journal
Cell death discovery
year
2023
abstract
Hypertrophic scar (HS) is an abnormal fibrous hyperplasia of the skin caused by excessive tissue repair in response to skin burns and trauma, which restricts physical function and impairs patients' quality of life. Numerous studies have shown that pressure garment therapy (PGT) is an effective treatment for preventing hypertrophic scars. Herein, we found that mechanical stress stimulates the neuropilin 1 (NRP1) expression through screening GSE165027, GSE137210, and GSE120194 from Gene Expression Omnibus (GEO) database and bioinformatics analysis. We verified this stimulation in the human hypertrophic scar, pressure culture cell model, and rat tail-scar model. Mechanical compression increased LATS1 and pYAP enrichment, thus repressing the expression of YAP. Functionally, the knockdown of NRP1 promoted the expression of LATS1, thus decreasing the expression of YAP and inhibiting endothelial cell proliferation. Furthermore, co-immunoprecipitation analysis confirmed that NRP1 binds to YAP, and mechanical compression disrupted this binding, which resulted in the promotion of YAP relocation to nuclear. In conclusion, our results indicated that NRP1 transduces mechanical force inhibition by inhibiting YAP expression. Mechanical pressure can release YAP bound to NRP1, which explains the phenomenon that mechanical stress increases YAP in the nucleus. Strategies targeting NRP1 may promote compression therapy with optimal and comfortable pressures.
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We then constructed a co-expression network using the WGCNA algorithm with the R package [28, 29]. Data filtering, original annotation, quality control, normalization, and DEG identification were performed in RStudio (version 1.2.5042) using the GEOquery, limma, stringr, and ggplot2 packages.
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ophic scar, pressure culture cell model, and rat tail-scar model. Mechanical compression incr
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Complete file
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Numerous studies have shown that pressure garment therapy (PGT) is an effective treatment for preventing hypertrophic scars. Herein, we found that mechanical stress stimulates the neuropilin 1 (NRP1) expression through screening GSE165027, GSE137210, and GSE120194 from Gene Expression Omnibus (GEO) database and bioinformatics analysis. We verified this stimulation in the human hypertrophic scar, pressure culture cell model, and rat tail-scar model. Mechanical compression increased LATS1 and pYAP enrichment, thus repressing the expression of YAP. Functionally, the knockdown of NRP1 promoted the expression of LATS1, thus decreasing the expression of YAP and inhibiting endothelial cell proliferation. Furthermore, co-immunoprecipitation analysis confirmed that NRP1 binds to YAP, and mechanical compression disrupted this binding, which resulted in the promotion of YAP relocation to nuclear. In conclusion, our results indicated that NRP1 transduces mechanical force inhibition by inhibiting YAP expression. Mechanical pressure can release YAP bound to NRP1, which explains the phenomenon that mechanical stress increases YAP in the nucleus. Strategies targeting NRP1 may promote compression therapy with optimal and comfortable pressures.", "claims": [{"id": "claim-method", "statement": "We then constructed a co-expression network using the WGCNA algorithm with the R package [28, 29]. 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