ArticleHepatology (Baltimore, Md.)2017
The unfolded protein response mediates fibrogenesis and collagen I secretion through regulating TANGO1 in mice.
Article in Hepatology (Baltimore, Md.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 107 citations in OpenAlex.
- The PERK-GADD45A axis is a key driver of hepatic stellate cell activation.Hepatology communications · 2026Article
- MSC-derived apoptotic vesicles remodel hepatic macrophage polarization and suppress fibrosis via miR-6869-5p-mediated inhibition of FGF1 and HMGB1.Journal of nanobiotechnology · 2026Article
- Endoplasmic reticulum and Golgi stress signaling-mediated regulation of protein secretion.Cellular & molecular biology letters · 2026Review
- FAM134B controls collagen I dynamics in hepatic stellate cell-driven fibrosis.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Targeting the ER stress sensor IRE1 protects the liver from fibrosis through the downregulation of the proteostasis factor P4HB/PDIA1.Hepatology (Baltimore, Md.) · 2026Article
- Gemigliptin Alleviates Succinate Induced Endoplasmic Reticulum Stress and Activation of Hepatic Stellate Cells.Journal of Korean medical science · 2025Article
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- Developments in the connection between epithelial‑mesenchymal transition and endoplasmic reticulum stress (Review).International journal of molecular medicine · 2025Review
- Identification of matrix stiffness-related molecular subtypes in HCC via integrating multi-omics analysis and machine learning algorithms.Journal of translational medicine · 2025Article
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- [Research progress on collagen secretion mechanisms in scarring].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025Review
- Unfolded protein responses: Dynamic machinery in wound healing.Pharmacology & therapeutics · 2025Review
- Endoplasmic Reticulum-Targeting Natural Compounds: A Novel Frontier in Alleviating Liver Fibrosis.Drug design, development and therapy · 2025Review
- Biomimetic mesenchymal stem cell membrane-coated nanoparticle delivery of MKP5 inhibits hepatic fibrosis through the IRE/XBP1 pathway.Journal of nanobiotechnology · 2024Article
- Article
- The effects of TGF-β-induced activation and starvation of vitamin A and palmitic acid on human stem cell-derived hepatic stellate cells.Stem cell research & therapy · 2024Article
- TANGO1 inhibitors reduce collagen secretion and limit tissue scarring.Nature communications · 2024Article
- TANGO6 regulates cell proliferation via COPI vesicle-mediated RPB2 nuclear entry.Nature communications · 2024Article
- Article
- Knockdown of Hyaluronan synthase 2 suppresses liver fibrosis in mice via induction of transcriptomic changes similar to 4MU treatment.Scientific reports · 2024Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Fibrogenesis encompasses the deposition of matrix proteins, such as collagen I, by hepatic stellate cells (HSCs) that culminates in cirrhosis. Fibrogenic signals drive transcription of procollagen I, which enters the endoplasmic reticulum (ER), is trafficked through the secretory pathway, and released to generate extracellular matrix. Alternatively, disruption of procollagen I ER export could activate the unfolded protein response (UPR) and drive HSC apoptosis. Using a small interfering RNA screen, we identified Transport and Golgi organization 1 (TANGO1) as a potential participant in collagen I secretion. We investigated the role of TANGO1 in procollagen I secretion in HSCs and liver fibrogenesis. Depletion of TANGO1 in HSCs blocked collagen I secretion without affecting other matrix proteins. Disruption of secretion led to procollagen I retention within the ER, induction of the UPR, and HSC apoptosis. In wild-type (WT) HSCs, both TANGO1 and the UPR were induced by transforming growth factor β (TGFβ). As the UPR up-regulates proteins involved in secretion, we studied whether TANGO1 was a target of the UPR. We found that UPR signaling is responsible for up-regulating TANGO1 in response to TGFβ, and this mechanism is mediated by the transcription factor X-box binding protein 1 (XBP1). In vivo, murine and human cirrhotic tissue displayed increased TANGO1 messenger RNA levels. Finally, TANGO1
conclusionLoss of TANGO1 leads to procollagen I retention in the ER, which promotes UPR-mediated HSC apoptosis. TANGO1 regulation during HSC activation occurs through a UPR-dependent mechanism that requires the transcription factor, XBP1. Finally, TANGO1 is critical for fibrogenesis through mediating HSC homeostasis. The work reveals a unique role for TANGO1 and the UPR in facilitating collagen I secretion and fibrogenesis. (Hepatology 2017;65:983-998).
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