ArticleJournal of cellular and molecular medicine2020
C-X-C motif chemokine receptor 4 aggravates renal fibrosis through activating JAK/STAT/GSK3β/β-catenin pathway.
Article in Journal of cellular and molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- The E3 ubiquitin ligase Itch plays an essential role in kidney fibrosis by inhibiting Dvl2/GSK3β/β-catenin signaling pathway.Cell death and differentiation · 2026Article
- Glycogen synthase kinase 3β: a key player in progressive chronic kidney disease.Clinical science (London, England : 1979) · 2025Review
- Albiflorin inhibits inflammation to improve liver fibrosis by targeting the CXCL12/CXCR4 axis in mice.Frontiers in pharmacology · 2025Article
- Natural products in traditional Chinese medicine for renal fibrosis: a comprehensive review.Frontiers in pharmacology · 2025Review
- Dual blockade of DPP-4 and CXCL12/CXCR4 axes synergistically protects podocytes in lupus nephritis.Frontiers in pharmacology · 2025Article
- Second Generation I-Body AD-214 Attenuates Unilateral Ureteral Obstruction (UUO)-Induced Kidney Fibrosis Through Inhibiting Leukocyte Infiltration and Macrophage Migration.International journal of molecular sciences · 2024Article
- CXC chemokine receptor 7 ameliorates renal fibrosis by inhibiting β-catenin signaling and epithelial-to-mesenchymal transition in tubular epithelial cells.Renal failure · 2024Article
- Cellular regenerative therapy in stress urinary incontinence: new frontiers?-a narrative review.Translational andrology and urology · 2024Review
- Review
- C-X-C chemokine receptor type 4 promotes tubular cell senescence and renal fibrosis through β-catenin-inhibited fatty acid oxidation.Journal of cellular and molecular medicine · 2024Article
- An updated review of the pharmacological effects and potential mechanisms of hederagenin and its derivatives.Frontiers in pharmacology · 2024Review
- GPCRs overexpression and impaired fMLP-induced functions in neutrophils from chronic kidney disease patients.Frontiers in immunology · 2024Article
- Review
- STAT-3 signaling role in an experimental model of nephropathy induced by doxorubicin.Molecular and cellular biochemistry · 2023Article
- Urinary exosomal miRNA-663a shows variable expression in diabetic kidney disease patients with or without proteinuria.Scientific reports · 2023Article
- The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention.Cellular & molecular immunology · 2023Review
- Loss of RTN3 phenocopies chronic kidney disease and results in activation of the IGF2-JAK2 pathway in proximal tubular epithelial cells.Experimental & molecular medicine · 2022Article
- CXCR4 promotes the growth and metastasis of esophageal squamous cell carcinoma as a critical downstream mediator of HIF-1α.Cancer science · 2022Article
- CXC Chemokine Receptor 2 Accelerates Tubular Cell Senescence and Renal FibrosisFrontiers in cell and developmental biology · 2022Article
- Cannabinoid receptor 2 plays a central role in renal tubular mitochondrial dysfunction and kidney ageing.Journal of cellular and molecular medicine · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic kidney disease (CKD) has a high prevalence worldwide. Renal fibrosis is the common pathological feature in various types of CKD. However, the underlying mechanisms are not determined. Here, we adopted different CKD mouse models and cultured human proximal tubular cell line (HKC-8) to examine the expression of C-X-C motif chemokine receptor 4 (CXCR4) and β-catenin signalling, as well as their relationship in renal fibrosis. In CKD mice and humans with a variety of nephropathies, CXCR4 was dramatically up-regulated in tubules, with a concomitant activation of β-catenin. CXCR4 expression level was positively correlated with the expression of β-catenin target MMP-7. AMD3100, a CXCR4 receptor blocker, and gene knockdown of CXCR4 significantly inhibited the activation of JAK/STAT and β-catenin signalling, protected against tubular injury and renal fibrosis. CXCR4-induced renal fibrosis was inhibited by treatment with ICG-001, an inhibitor of β-catenin signalling. In HKC-8 cells, overexpression of CXCR4 induced activation of β-catenin and deteriorated cell injury. These effects were inhibited by ICG-001. Stromal cell-derived factor (SDF)-1α, the ligand of CXCR4, stimulated the activation of JAK2/STAT3 and JAK3/STAT6 signalling in HKC-8 cells. Overexpression of STAT3 or STAT6 decreased the abundance of GSK3β mRNA. Silencing of STAT3 or STAT6 significantly blocked SDF-1α-induced activation of β-catenin and fibrotic lesions. These results uncover a novel mechanistic linkage between CXCR4 and β-catenin activation in renal fibrosis in association with JAK/STAT/GSK3β pathway. Our studies also suggest that targeted inhibition of CXCR4 may provide better therapeutic effects on renal fibrosis by inhibiting multiple downstream signalling cascades.
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