ArticleThe Journal of clinical investigation2021
Endoplasmic reticulum protein TXNDC5 promotes renal fibrosis by enforcing TGF-β signaling in kidney fibroblasts.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 102 citations in OpenAlex.
- Comparison of the efficacy of TXNDC5 monoclonal antibody versus conventional drugs in the treatment of intestinal fibrosis associated with inflammatory bowel disease.Journal of molecular histology · 2026Article
- Mitochondrial dysfunction of renal tubular epithelial cells in chronic kidney disease-associated fibrosis: from organelle homeostasis to multicellular remodeling.Molecular biology reports · 2026Review
- Endoplasmic reticulum stress exacerbates ischemia-reperfusion-induced pulmonary endothelial barrier dysfunction by activating TXNDC5.Journal of advanced research · 2026Article
- Targeting NAT10 with Remodelin reshapes the pro-fibrotic microenvironment in renal fibrogenesisActa pharmaceutica Sinica. B · 2026Article
- EVA1A responds to endoplasmic reticulum stress to regulate renal fibrosis by promoting TGF-β signaling pathway.Journal of advanced research · 2026Article
- Targeting fibroblast TXNDC5 resolves tumor desmoplasia and PD-1 resistance in colorectal cancer with mesenchymal traits.Nature communications · 2026Article
- Cyclosporine A promotes renal fibrosis through activating endoplasmic reticulum stress by targeting miR-212-5p/ATF6 axis.Journal of translational medicine · 2026Article
- Review
- TXNDC5 in POAG: Promoting Extracellular Matrix Protein Accumulation and Raising Intraocular Pressure.Investigative ophthalmology & visual science · 2026Article
- Intercellular Horizontal Transfer of TXNDC5 mRNA via Extracellular Vesicles Contributes to Tumor-Associated Macrophage-Mediated Prostate Cancer Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Novel AI-Driven Precision Strategies in Diabetic Wound Healing: Immunomodulation and Advances in Smart Composite Nanocarriers.Pharmaceutics · 2026Review
- ATF3 aggravates kidney fibrosis via HDAC6-dependent epigenetic reprogramming.International journal of biological sciences · 2026Article
- Interpretable Machine Learning Identifies Hub Biomarkers of Renal Fibrosis and Their Potential Medical Applications.Drug design, development and therapy · 2026Article
- Axolotl-derived decellularized skin ECM as a pro-regenerative scaffold for attenuating fibrotic wound healing.Materials today. Bio · 2025Article
- Lactate orchestrates the TGFβ pathway and ferroptosis nexus in organ fibrosis via USP2 lactylation.Communications biology · 2025Article
- INHBA knockdown inhibits renal fibrosis in mice following ischemia-reperfusion injury by suppressing activation of the TGF-β/Smad signaling pathway.BMC nephrology · 2025Article
- NAT10 Mediates Cardiac Fibrosis Induced by Myocardial Infarction Through ac4C Modification of TGFBR1 mRNA.Cell biology and toxicology · 2025Article
- GPX3 promotes cisplatin resistance in TNBC by manipulating ROS-TGFB1-ZEB2.Cell communication and signaling : CCS · 2025Article
- Deletion of TXNDC5 downregulates TGFβ1-αSMA-mediated testicular fibrosis in mice.Reproduction (Cambridge, England) · 2025Article
- The PERK/ATF4 pathway is required for metabolic reprogramming and progressive lung fibrosis.JCI insight · 2025Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Renal fibrosis, a common pathological manifestation of virtually all types of chronic kidney disease (CKD), often results in diffuse kidney scarring and predisposes to end-stage renal disease. Currently, there is no effective therapy against renal fibrosis. Recently, our laboratory identified an ER-resident protein, thioredoxin domain containing 5 (TXNDC5), as a critical mediator of cardiac fibrosis. Transcriptome analyses of renal biopsy specimens from patients with CKD revealed marked TXNDC5 upregulation in fibrotic kidneys, suggesting a potential role of TXNDC5 in renal fibrosis. Employing multiple fluorescence reporter mouse lines, we showed that TXNDC5 was specifically upregulated in collagen-secreting fibroblasts in fibrotic mouse kidneys. In addition, we showed that TXNDC5 was required for TGF-β1-induced fibrogenic responses in human kidney fibroblasts (HKFs), whereas TXNDC5 overexpression was sufficient to promote HKF activation, proliferation, and collagen production. Mechanistically, we showed that TXNDC5, transcriptionally controlled by the ATF6-dependent ER stress pathway, mediated its profibrogenic effects by enforcing TGF-β signaling activity through posttranslational stabilization and upregulation of type I TGF-β receptor in kidney fibroblasts. Using a tamoxifen-inducible, fibroblast-specific Txndc5 knockout mouse line, we demonstrated that deletion of Txndc5 in kidney fibroblasts mitigated the progression of established kidney fibrosis, suggesting the therapeutic potential of TXNDC5 targeting for renal fibrosis and CKD.
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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.