ArticleJCI insight2020
Free light chains injure proximal tubule cells through the STAT1/HMGB1/TLR axis.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- IgG Glycosylation-Dependent CLEC7A Signaling Drives Podocyte Dysfunction in Lupus Nephritis.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Lipids in kidney diseases: from systemic imbalance to intrarenal alterations of cellular lipid metabolism in rare and common kidney diseases.Journal of molecular medicine (Berlin, Germany) · 2026Review
- TRMT13 inhibits the growth of papillary thyroid cancer by targeting ANAPC4.Acta biochimica et biophysica Sinica · 2024Article
- The STAT1/HMGB1/NF-κB pathway in chronic inflammation and kidney injury after cisplatin exposure.Theranostics · 2023Article
- Targeting HMGB1: A Potential Therapeutic Strategy for Chronic Kidney Disease.International journal of biological sciences · 2023Review
- The potential link between Covid-19 and multiple myeloma: A new saga.Immunity, inflammation and disease · 2022Review
- Aristolochic acid I induces proximal tubule injury through ROS/HMGB1/mt DNA mediated activation of TLRs.Journal of cellular and molecular medicine · 2022Article
- Signaling pathways of chronic kidney diseases, implications for therapeutics.Signal transduction and targeted therapy · 2022Review
- The innate immune system in human kidney inflammaging.Journal of nephrology · 2022Review
- Chronic Kidney Disease and Cancer: Inter-Relationships and Mechanisms.Frontiers in cell and developmental biology · 2022Review
- Transgelin-2 in Multiple Myeloma: A New Marker of Renal Impairment?Molecules (Basel, Switzerland) · 2021Article
- Cell spinpods are a simple inexpensive suspension culture device to deliver fluid shear stress to renal proximal tubular cells.Scientific reports · 2021Article
- Cellular antioxidant mechanisms control immunoglobulin light chain-mediated proximal tubule injury.Free radical biology & medicine · 2021Article
- The Proximal Tubule Toxicity of Immunoglobulin Light Chains.Kidney international reports · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Free light chains (FLCs) induce inflammatory pathways in proximal tubule cells (PTCs). The role of TLRs in these responses is unknown. Here we present findings on the role of TLRs in FLC-induced PTC injury. We exposed human kidney PTC cultures to κ and λ FLCs and used cell supernatants and pellets for ELISA and gene expression studies. We also analyzed tissues from Stat1-/- and littermate control mice treated with daily i.p. injections of a κ FLC for 10 days. FLCs increased the expression of TLR2, TLR4, and TLR6 via HMGB1, a damage-associated molecular pattern. Countering TLR2, TLR4, and TLR6 through GIT-27 or specific TLR siRNAs reduced downstream cytokine responses. Blocking HMGB1 through siRNA or pharmacologic inhibition, or via STAT1 inhibition, reduced FLC-induced TLR2, TLR4, and TLR6 expression. Blocking endocytosis of FLCs through silencing of megalin/cubilin, with bafilomycin A1 or hypertonic sucrose, attenuated FLC-induced cytokine responses in PTCs. IHC showed decreased TLR4 and TLR6 expression in kidney sections from Stat1-/- mice compared with their littermate controls. PTCs exposed to FLCs released HMGB1, which induced expression of TLR2, TLR4, and TLR6 and downstream inflammation. Blocking FLCs' endocytosis, Stat1 knockdown, HMGB1 inhibition, and TLR knockdown each rescued PTCs from FLC-induced injury.
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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.