ArticleJournal of cellular and molecular medicine2020
Tacrolimus ameliorates tubulointerstitial inflammation in diabetic nephropathy via inhibiting the NFATc1/TRPC6 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. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Article
- Unlocking the therapeutic potential of the NFAT pathway in kidney diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Anti-Fibrotic Effect of Tacrolimus on Preventing Adhesion after Achilles Tendon Surgery in a Murine Model.Iranian journal of medical sciences · 2025Article
- Tacrolimus and diabetic rodent models.Pharmacological reports : PR · 2025Review
- PIEZO1-Mediated Calcium Signaling and Podocyte Injury in Diabetic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2025Article
- Programmed Cell Death in Diabetic Kidney Disease: Mechanisms and Therapeutic Targeting.Journal of inflammation research · 2025Review
- The roles of TRPC6 in renal tubular disorders: a narrative review.Renal failure · 2024Review
- TRPC6-Calpain-1 Axis Promotes Tubulointerstitial Inflammation by Inhibiting Mitophagy in Diabetic Kidney Disease.Kidney international reports · 2024Article
- Rituximab Combined with Steroid and Tacrolimus Treats Proliferative Glomerulonephritis with Monoclonal IgG Deposits: A Case Report and Review of the Literature.Current medicinal chemistry · 2024Review
- A Putative Role for TRPC6 in Immune-Mediated Kidney Injury.International journal of molecular sciences · 2023Review
- Cordycepin from Cordyceps militaris ameliorates diabetic nephropathy via the miR-193b-5p/MCL-1 axis.Chinese medicine · 2023Article
- Inhalation of ACE2 as a therapeutic target on sex-bias differences in SARS-CoV-2 infection and variant of concern.iScience · 2023Article
- microRNA-29b-3p attenuates diabetic nephropathy in mice by modifying EZH2.Hormones (Athens, Greece) · 2023Article
- Epsin1-mediated exosomal sorting of Dll4 modulates the tubular-macrophage crosstalk in diabetic nephropathy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Identification of transcription factors related to diabetic tubulointerstitial injury.Journal of translational medicine · 2023Article
- NETosis: an emerging therapeutic target in renal diseases.Frontiers in immunology · 2023Review
- lncRNA MALAT1 Promotes Diabetic Nephropathy Progression via miR-15b-5p/TLR4 Signaling Axis.Journal of immunology research · 2022Article
- Tacrolimus ameliorates tubulointerstitial inflammation in diabetic nephropathy via inhibiting the NFATc1/TRPC6 pathway.Journal of cellular and molecular medicine · 2020Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tubulointerstitial inflammation is crucial for the progression of diabetic nephropathy (DN), and tubular cells act as a driving force in the inflammatory cascade. Emerging data suggested that tacrolimus (TAC) ameliorates podocyte injury and macrophage infiltration in streptozotocin (STZ) mice. However, the effect of TAC on tubulointerstitial inflammation remains unknown. We found that albuminuria and tubulointerstitial damage improved in db/db mice treated with TAC. Macrophage infiltration and expression of IL-6, TNF-α, fibronectin, collagen 1 and cleaved caspase 3 were inhibited as well. In addition, the expression of nuclear factor of activated T cell 1 (NFATc1) and transient receptor potential channel 6 (TRPC6) was up-regulated in the kidneys of DN patients and correlated with tubular injury and inflammation. The expression of NFATc1 and TRPC6 also increased in the kidneys of db/db mice and HK-2 cells with high glucose (HG), while TAC inhibited these effects. HG-induced inflammatory markers and apoptosis were reversed by TAC and NFATc1 siRNA in HK-2 cells, which was abolished by TRPC6 plasmid. Furthermore, HG-induced TRPC6 expression was inhibited by NFATc1 siRNA, while NFATc1 nuclear translocation was inhibited by TAC, but was restored by TRPC6 plasmid in HK-2 cells under HG conditions. These findings suggest that TAC ameliorates tubulointerstitial inflammation in DN through NFATc1/TRPC6 feedback loop.
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