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Results for “4D label-free quantitative proteomics”

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PubMed2026

Integrated LiP-MS and quantitative proteomics reveal coordinated alterations in protein conformation and expression across tumor and peritumoral regions in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) exhibits substantial molecular heterogeneity, yet protein-level alterations beyond abundance remain insufficiently characterized. Here, we integrated limited proteolysis mass spectrometry (Lip-MS) with 4D label-free quantitative proteomics to investigate conformational accessibility and protein abundance across tumor, peritumoral-near, and peritumoral-far tissues from HCC patients. Differential LiP peptides identified by both DDA and DIA corresponded to 725, 674, and 33 differentially conformed proteins in the Tumor vs. Peritumor-far, Tumor vs. Peritumor-near, and Peritumor-near vs. Peritumor-far comparisons, respectively. Quantitative proteomics identified 405, 365, and 4 differentially expressed proteins in the corresponding comparisons. Integrated analysis identified 488 and 469 conformation-specific altered proteins (CSAPs), which showed altered conformational accessibility without significant abundance changes, and 237 and 205 conformation-expression coupled proteins (CECPs) in the two tumor-involved comparisons. LiP peptide and protein abundance changes were positively correlated, with Spearman coefficients of 0.69-0.72, and more than 99% of CECPs showed concordant directions. Among them, 169 region-conserved CECPs (rcCECPs) were predominantly associated with metabolic and redox-related pathways. Protein-protein interaction analysis identified 30 hub rcCECPs. ACLY, ALDH18A1, GMPS, and DHX9 showed increased representative LiP peptide signals and protein abundance, elevated transcript expression in HCC, and associations with poorer overall survival. Peptide mapping further localized their differential LiP signals to specific sequence regions and annotated domains. Collectively, these findings provide an integrated view of regional conformational accessibility and protein abundance alterations in HCC and identify candidate proteins for further structural and functional investigation.

Humans↗

PubMed2025

Corticotropin-releasing hormone inhibits autophagy by suppressing PTEN to promote apoptosis in dermal papilla cells.

BACKGROUND: Stress-related hair loss is on the rise, largely due to escalating levels of stress-related corticotropin-releasing hormone (CRH) through poorly defined mechanisms. CRH-mediated activation of corticotropin-releasing hormone receptors (CRHRs) on dermal papilla cells (DPCs) is a likely cause of stress-related hair loss. The aim of the study is to elucidate the key mechanisms of alopecia caused by CRH and provide potential new targets for the treatment of stress-related hair loss. METHODS: 4D label-free quantitative proteomics of DPCs and the chronic unpredictable mild stress mouse (CUMS) model were used to explore the relationship and mechanism between CRH, DPCs and hair regeneration. RESULTS: CRH initially downregulated PTEN to suppress autophagy, leading to DPC apoptosis. Overexpression of PTEN enhanced autophagy and mitigated CRH-dependent DPC apoptosis. CRH inhibited PTEN and activated the PI3K/AKT/mTOR pathway, whereas rapamycin inhibited this pathway and activated autophagy, consequently lowering apoptosis, suggesting that increased susceptibility to apoptosis is caused by decreased autophagy. CUMS-induced hair growth disruption is accompanied by an increase in CRHRs and a decrease in PTEN levels within the dermal papilla. Intracutaneous injection of CRH impeded hair regeneration and decreased PTEN in mice, concurrent with inhibition of autophagy and increased apoptosis. CONCLUSIONS: These findings indicate that PTEN loss coupled with PI3K/AKT/mTOR-mediated autophagy inhibition and apoptosis in DPCs is a key mechanism of stress-related hair loss induced by CRH and suggests that topical activation of PTEN or enhancement of autophagy, e.g. through rapamycin, may have a therapeutic effect on stress-induced hair loss disorders such as alopecia.

Animals↗