ArticleSignal transduction and targeted therapy2020
A novel role of LRP5 in tubulointerstitial fibrosis through activating TGF-β/Smad signaling.
Article in Signal transduction and targeted therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- New findings in diabetic kidney disease: correlation and enhanced combined diagnostic value of sclerostin and 25(OH)VD.Frontiers in endocrinology · 2026Article
- Review
- Human adipose-derived mesenchymal stem cell-derived exosomes induce epithelial remodeling and anti-scar healing revealed by single-cell RNA sequencing.Journal of nanobiotechnology · 2025Article
- Pathogenesis and Therapeutic Perspectives of Tubular Injury in Diabetic Kidney Disease: An Update.Biomedicines · 2025Review
- Wnt/β-catenin signaling pathway: proteins' roles in osteoporosis and cancer diseases and the regulatory effects of natural compounds on osteoporosis.Molecular medicine (Cambridge, Mass.) · 2024Review
- Ailanthone ameliorates pulmonary fibrosis by suppressing JUN-dependent MEOX1 activation.Acta pharmaceutica Sinica. B · 2024Article
- LDL receptor-related protein 5 selectively transports unesterified polyunsaturated fatty acids to intracellular compartments.Nature communications · 2024Article
- Association of oxidative balance score with chronic kidney disease: NHANES 1999-2018.Frontiers in endocrinology · 2024Article
- Article
- Integrating Common Risk Factors with Polygenic Scores Improves the Prediction of Type 2 Diabetes.International journal of molecular sciences · 2023Article
- Alpha-lipoic acid could attenuate the effect of chemerin-induced diabetic nephropathy progression.Iranian journal of basic medical sciences · 2021Article
- Distinct roles of LRP5 and LRP6 in Wnt signaling regulation in the retina.Biochemical and biophysical research communications · 2021Article
- Exosomes: Biomarkers and Therapeutic Targets of Diabetic Vascular Complications.Frontiers in endocrinology · 2021Review
- Icariin Ameliorates Diabetic Renal Tubulointerstitial Fibrosis by Restoring AutophagyFrontiers in pharmacology · 2021Article
- PPARγ Mediates the Anti-Epithelial-Mesenchymal Transition Effects of FGF1Frontiers in pharmacology · 2021Article
- LRP5 and LRP6 in Wnt Signaling: Similarity and Divergence.Frontiers in cell and developmental biology · 2021Review
- Network Pharmacology and Experimental Assessment to Explore the Pharmacological Mechanism of Qimai Feiluoping Decoction Against Pulmonary Fibrosis.Frontiers in pharmacology · 2021Article
- LRP5-Mediated Lipid Uptake Modulates Osteogenic Differentiation of Bone Marrow Mesenchymal Stromal Cells.Frontiers in cell and developmental biology · 2021Article
- Article
- Dexmedetomidine Protects Against Kidney Fibrosis in Diabetic Mice by Targeting miR-101-3p-Mediated EndMT.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Previous studies by us and others demonstrated that activation of Wnt/β-catenin signaling plays a pathogenic role in chronic kidney diseases (CKD). Wnt co-receptor LRP5 variants are reported to associate with autosomal dominant polycystic kidney disease; but their exact roles in this disease and renal fibrosis have not been explored. Here, we observed the upregulation of LRP5 in the renal tubules of both type 1 and type 2 diabetic models and of an obstructive nephropathy model. In the obstructed kidneys, Lrp5 knockout significantly ameliorated tubulointerstitial fibrosis and tubular injury without changing Wnt/β-catenin signaling. Instead, decreased levels of TGF-β1 and TGF-β receptors (TβRs) were detected in Lrp5 knockout kidneys, followed by attenuated activation and nuclear translocation of Smad2/3 in the renal tubules, suggesting a regulatory effect of LRP5 on TGF-β/Smad signaling. In consistent with this hypothesis, LRP5 overexpression resulted in enhanced TGF-β/Smad signaling activation in renal tubule epithelial cells. Furthermore, LRP5 was co-immunoprecipitated with TβRI and TβRII, and its extracellular domain was essential for interacting with TβRs and for its pro-fibrotic activity. In addition to stabilizing TβRs, LRP5 increased the basal membrane presentation and TGF-β1-induced internalization of these receptors. Notably, TGF-β1 also induced LRP5 internalization. These findings indicate that LRP5 promotes tubulointerstitial fibrosis, at least partially, via direct modulation of TGF-β/Smad signaling, a novel, Wnt-independent function.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.