ArticleThe Journal of biological chemistry2017
A small-molecule compound inhibits a collagen-specific molecular chaperone and could represent a potential remedy for fibrosis.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 73 citations in OpenAlex.
- Collagen-specific molecular chaperone Hsp47 in inguinal white adipose tissue promotes high-fat diet-induced inflammatory gene expression in male mice.Scientific reports · 2026Article
- Beyond Structure: The Dynamic Role of the Extracellular Matrix Components in Immune Evasion.Cancer communications (London, England) · 2026Review
- HSP47 inhibition-induced CD155 expression through TRAF2 deubiquitination promotes tumor immune evasion.Journal for immunotherapy of cancer · 2025Article
- A collagenous extracellular matrix regulates germline gene expression in the sea star embryo.Scientific reports · 2025Article
- Potential Modulatory Effects of β-Hydroxy-β-Methylbutyrate on Type I Collagen Fibrillogenesis: Preliminary Study.International journal of molecular sciences · 2025Article
- Targeting collagen in "armored and cold" tumors: Overcoming barriers to cancer therapy.Cancer pathogenesis and therapy · 2025Review
- Targeting collagen to optimize cancer immunotherapy.Experimental hematology & oncology · 2025Review
- Hsp47 drives obesity-associated breast cancer progression by enhancing asporin deposition in adipose tissue.Breast cancer research : BCR · 2025Article
- The Role of HSP47 in Thrombotic Disorders: Molecular Mechanism and Therapeutic Potential.Current issues in molecular biology · 2025Review
- Targeting the HSP47-collagen axis inhibits brain metastasis by reversing M2 microglial polarization and restoring anti-tumor immunity.Cell reports. Medicine · 2024Article
- Integrated analysis of tumor and adjacent non-tumor proteomic data reveals SERPINH1 as a recurrence biomarker and drug target in hepatocellular carcinoma.International journal of biological sciences · 2024Article
- Multiple aspects of matrix stiffness in cancer progression.Frontiers in oncology · 2024Review
- HSP47 levels determine the degree of body adiposity.Nature communications · 2023Article
- HSP47: A Therapeutic Target in Pulmonary Fibrosis.Biomedicines · 2023Review
- Therapeutic Strategies to Overcome Fibrotic Barriers to Nanomedicine in the Pancreatic Tumor Microenvironment.Cancers · 2023Review
- Effectiveness of conjunctival bleb scarring by knock-down of heat shock protein 47 in rat model.International journal of ophthalmology · 2023Article
- Platelets in the tumor microenvironment and their biological effects on cancer hallmarks.Frontiers in oncology · 2023Review
- Collagen Remodeling along Cancer Progression Providing a Novel Opportunity for Cancer Diagnosis and Treatment.International journal of molecular sciences · 2022Review
- Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy.Journal of hematology & oncology · 2022Review
- Collagen XI Alpha 1 Chain, a Novel Therapeutic Target for Cancer Treatment.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibrosis can disrupt tissue structure and integrity and impair organ function. Fibrosis is characterized by abnormal collagen accumulation in the extracellular matrix. Pharmacological inhibition of collagen secretion therefore represents a promising strategy for the management of fibrotic disorders, such as liver and lung fibrosis. Hsp47 is an endoplasmic reticulum (ER)-resident collagen-specific molecular chaperone essential for correct folding of procollagen in the ER. Genetic deletion of Hsp47 or inhibition of its interaction with procollagen interferes with procollagen triple helix production, which vastly reduces procollagen secretion from fibroblasts. Thus, Hsp47 could be a potential and promising target for the management of fibrosis. In this study, we screened small-molecule compounds that inhibit the interaction of Hsp47 with collagen from chemical libraries using surface plasmon resonance (BIAcore), and we found a molecule AK778 and its cleavage product Col003 competitively inhibited the interaction and caused the inhibition of collagen secretion by destabilizing the collagen triple helix. Structural information obtained with NMR analysis revealed that Col003 competitively binds to the collagen-binding site on Hsp47. We propose that these structural insights could provide a basis for designing more effective therapeutic drugs for managing fibrosis.
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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 OpenQuestion graph.