ArticleJournal of cellular and molecular medicine2015
The IκB kinase inhibitor ACHP strongly attenuates TGFβ1-induced myofibroblast formation and collagen synthesis.
Article in Journal of cellular and molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- In Vitro Assessment of Nintedanib in Keratoconus Corneal Stromal Microenvironment.Biomolecules · 2026Article
- Effects of moderate doses of ionizing radiation on experimental abdominal aortic aneurysm.PloS one · 2024Article
- Procollagen-lysine 2-oxoglutarate 5-dioxygenases are responsible for 5R-hydroxylysine modification of therapeutic T-cell bispecific monoclonal antibodies produced by Chinese hamster ovary cells.Frontiers in bioengineering and biotechnology · 2024Article
- Identification of lactylation related model to predict prognostic, tumor infiltrating immunocytes and response of immunotherapy in gastric cancer.Frontiers in immunology · 2023Article
- NF-кB c-Rel modulates pre-fibrotic changes in human fibroblasts.Archives of dermatological research · 2022Article
- Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 increases cellular proliferation and colony formation capacity in lung cancer via activation of E2F transcription factor 1.Oncology letters · 2021Article
- Serum from Patients with Severe Alcoholic Liver Cirrhosis Inhibits Proliferation and Migration of Human Coronary Artery Smooth Muscle Cells.Journal of clinical medicine · 2021Article
- Fibroblast-specific IKK-β deficiency ameliorates angiotensin II-induced adverse cardiac remodeling in mice.JCI insight · 2021Article
- CD148 Deficiency in Fibroblasts Promotes the Development of Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2021Article
- Synovial Fibrosis Involvement in Osteoarthritis.Frontiers in medicine · 2021Review
- A novel positive feedback-loop between the HTLV-1 oncoprotein Tax and NF-κB activity in T-cells.Retrovirology · 2020Article
- Receptor tyrosine kinase ligands and inflammatory cytokines cooperatively suppress the fibrogenic activity in temporomandibular-joint-derived fibroblast-like synoviocytes via mitogen-activated protein kinase kinase/extracellular signal-regulated kinase.Experimental and therapeutic medicine · 2020Article
- The IκB Kinase Inhibitor ACHP Targets the STAT3 Signaling Pathway in Human Non-Small Cell Lung Carcinoma Cells.Biomolecules · 2019Article
- Topical Application of a Dual ABC Transporter Substrate and NF-κB Inhibitor Blocks Multiple Sources of Cutaneous Inflammation in Mouse Skin.The Journal of investigative dermatology · 2019Article
- Quantitative proteomic profiling of extracellular matrix and site-specific collagen post-translational modifications in anMatrix biology plus · 2019Article
- YAP activation promotes the transdifferentiation of cardiac fibroblasts to myofibroblasts in matrix remodeling of dilated cardiomyopathy.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2018Article
- The calcium channel proteins ORAI3 and STIM1 mediate TGF-β inducedOncotarget · 2018Article
- Roles of PLODs in Collagen Synthesis and Cancer Progression.Frontiers in cell and developmental biology · 2018Review
- Inhibition of IκB Kinase at 24 Hours After Acute Kidney Injury Improves Recovery of Renal Function and Attenuates Fibrosis.Journal of the American Heart Association · 2017Article
- Regulatory mechanisms of TGF-β1-induced fibrogenesis of human alveolar epithelial cells.Journal of cellular and molecular medicine · 2016Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Excessive accumulation of a collagen-rich extracellular matrix (ECM) by myofibroblasts is a characteristic feature of fibrosis, a pathological state leading to serious organ dysfunction. Transforming growth factor beta1 (TGFβ1) is a strong inducer of myofibroblast formation and subsequent collagen production. Currently, there are no remedies for the treatment of fibrosis. Activation of the nuclear factor kappa B (NF-κB) pathway by phosphorylating IκB with the enzyme IκB kinase (IKK) plays a major role in the induction of fibrosis. ACHP {2-Amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-(4-piperidinyl)-3 pyridinecarbonitrile}, a selective inhibitor of IKK, prohibits the activation of the NF-κB pathway. It is not known whether ACHP has potential anti-fibrotic properties. Using adult human dermal and lung fibroblasts we have investigated whether ACHP has the ability to inhibit the TGFβ1-induced transition of fibroblasts into myofibroblasts and its excessive synthesis of ECM. The presence of ACHP strongly suppressed the induction of the myofibroblast markers alpha-smooth muscle actin (αSMA) and SM22α, as well as the deposition of the ECM components collagen type I and fibronectin. Furthermore, post-treatment with ACHP partly reversed the expression of αSMA and collagen type I production. Finally, ACHP suppressed the expression of the three collagen-modifying enzymes lysyl hydroxylase (PLOD1, PLOD2 and PLOD3) in dermal fibroblasts, but did not do so in lung fibroblasts. We conclude that the IKK inhibitor ACHP has potent antifibrotic properties, and that the NF-κB pathway plays an important role in myofibroblast biology.
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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.