ArticleMolecular and cellular biochemistry2026
Deubiquitinase OTUD5 facilitates stiffness-induced hepatic stellate cell activation by stabilizing YAP.
Article in Molecular and cellular biochemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- Matrix stiffness may drive multi-cellular crosstalk via YAP signaling in biliary atresia liver fibrosis: a mechanistic review.Frontiers in cell and developmental biology · 2026Review
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Authors and funding
6 authors.
Funding
Abstract
Hepatic stellate cells (HSCs) activate and transdifferentiate into tumor-promoting myofibroblasts, which is an essential cause of colorectal liver metastasis. In addition to cytokines such as transforming growth factor-β, matrix stiffness is also a vital factor for promoting HSC activation. Our recent study reveals that OTU deubiquitinase 5 (OTUD5) promotes hepatocellular carcinoma progression, but its role and molecular mechanism in stiffness-induced HSC activation remain unclear. Polyacrylamide hydrogels with different composition ratios were used to simulate different matrix stiffnesses. Western blotting and immunofluorescence were performed to detect OTUD5, α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), Yes-associated protein (YAP), cysteine-rich angiogenic inducer 61 (CYR61), HA, FLAG, ubiquitin (UB), and MYC levels. RT-qPCR was used to assess the expression of OTUD5, YAP, CYR61, and CTGF mRNA. The interaction between OTUD5 and YAP, as well as the YAP ubiquitination level, was determined using a co-immunoprecipitation assay. The proliferation and invasion of HT-29 cells were determined by CCK-8 and transwell assays. The nude mouse subcutaneous co-injection model was used to evaluate the growth of HT-29 cells in vivo. HSCs cultured on a stiff substrate (11 kPa) showed significantly higher OTUD5 expression compared to those in the soft substrate (2 kPa). OTUD5 knockdown prominently attenuated stiffness-induced HSC activation. The stiffness-induced increase in OTUD5 expression was significantly abolished by YAP knockdown in HSCs. YAP overexpression enhanced, while YAP knockdown and inhibition reduced OTUD5 expression. In turn, OTUD5 positively regulated YAP protein level and YAP target genes, such as CYR61 and CTGF, in HSCs. Co-immunoprecipitation and immunofluorescence assays confirmed the interaction between OTUD5 and YAP. Mechanistically, OTUD5 functioned as a deubiquitinase, removing the K48 ubiquitin chain from YAP and maintaining protein stability. Functionally, OTUD5 knockdown markedly attenuated HSCs-induced HT-29 cell proliferation and invasion in vitro and tumor growth in vivo. Our results highlight the critical role of OTUD5/YAP feedback loop in stiffness-induced HSC activation, offering a potential therapeutic target for colorectal liver metastasis.
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41324862What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.