ArticleThe American journal of pathology2023
Renal Fibrosis Is Alleviated through Targeted Inhibition of IL-11-Induced Renal Tubular Epithelial-to-Mesenchymal Transition.
Article in The American journal of pathology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Interleukin-11 Signaling in Liver Disease: Mechanisms, Cellular Crosstalk, and Therapeutic Potential.Biomolecules · 2026Review
- Micheliolide suppresses epithelial-mesenchymal transition of lens epithelial cells via downregulating matrix metalloproteinase 8 to ameliorate posterior capsular opacification.Journal of translational medicine · 2026Article
- miR-204-5p attenuates inflammatory infiltration in early-stage chronic renal allograft dysfunction by modulating the IL-11/ERK1/2-NF-κB axis.Frontiers in immunology · 2026Article
- Inflammatory bowel disease and renal disorders: from clinical associations to shared mechanisms and management strategies.Frontiers in immunology · 2026Review
- The role of IL-11 in chronic diseases.Frontiers in immunology · 2026Review
- Metformin attenuates endoplasmic reticulum stress in diabetic kidney disease: mechanistic insights and future perspectives.International urology and nephrology · 2025Review
- Aging-associated interleukin-11 drives the molecular mechanism and targeted therapy of idiopathic pulmonary fibrosis.European journal of medical research · 2025Review
- Advances and challenges in kidney fibrosis therapeutics.Nature reviews. Nephrology · 2025Review
- Micheliolide Alleviates Hepatic Fibrosis by Inhibiting Autophagy in Hepatic Stellate Cells via the TrxR1/2-Mediated ROS/MEK/ERK Pathway.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Targeting Fibrosis: From Molecular Mechanisms to Advanced Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Mesenchymal stem cells suppress kidney injury molecule-1 associated with inhibition of renal PKC/NF-Kβ/STAT3 fibrotic signaling pathway in rats with diabetic nephropathy.Archives of medical science : AMS · 2025Article
- Renal tubular epithelial cells response to injury in acute kidney injury.EBioMedicine · 2024Review
- Depleting profibrotic macrophages using bioactivated in vivo assembly peptides ameliorates kidney fibrosis.Cellular & molecular immunology · 2024Article
- Fibroblast-derived interleukin-6 exacerbates adverse cardiac remodeling after myocardial infarction.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2024Article
- Pharmacological potential of micheliolide: A focus on anti-inflammatory and anticancer activities.Heliyon · 2024Review
- Understanding interleukin 11 as a disease gene and therapeutic target.The Biochemical journal · 2023Review
- The Pathobiology of IL-11 in Kidney Disease: From Epithelial Cell to Fibroblast and Back Again.The American journal of pathology · 2023Article
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10 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Renal fibrosis is a pathologic process that leads to irreversible renal failure without effective treatment. Epithelial-to-mesenchymal transition (EMT) plays a key role in this process. The current study found that aberrant expression of IL-11 is critically involved in tubular EMT. IL-11 and its receptor subunit alpha-1 (IL-11Rα1) were significantly induced in renal tubular epithelial cells (RTECs) in unilateral ureteral obstruction (UUO) kidneys, co-localized with transforming growth factor-β1. IL-11 knockdown ameliorated UUO-induced renal fibrosis in vivo and transforming growth factor-β1-induced EMT in vitro. IL-11 intervention directly induced the transdifferentiation of RTECs to the mesenchymal phenotype and increased the synthesis of profibrotic mediators. The EMT response induced by IL-11 was dependent on the sequential activation of STAT3 and extracellular signal-regulated kinase 1/2 signaling pathways and the up-regulation of metadherin in RTECs. Micheliolide (MCL) competitively inhibited the binding of IL-11 with IL-11Rα1, suppressing the activation of STAT3 and extracellular signal-regulated kinase 1/2-metadherin pathways, ultimately inhibiting renal tubular EMT and interstitial fibrosis induced by IL-11. In addition, treatment with dimethylaminomicheliolide, a pro-drug of MCL for in vivo use, significantly ameliorated renal fibrosis exacerbated by IL-11 in the UUO model. These findings suggest that IL-11 is a promising target in renal fibrosis and that MCL/dimethylaminomicheliolide exerts its antifibrotic effect by suppressing IL-11/IL-11Rα1 interaction and blocking its downstream effects.
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