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• W2119320021 abstract "Glomerulopathic light chains (LCs) are associated with two distinct mesangiopathies: AL (light-chain-related) amyloidosis and light-chain deposition disease (LCDD) with immunomorphologic features that are well documented in the literature. Even though both conditions are caused by monoclonal LCs, these entities differ dramatically in their morphologic expressions. In AL amyloidosis the mesangial matrix is replaced by amyloid fibrils, while in LCDD the matrix increases as a consequence of deposition of excess extracellular matrix (ECM). The immunomorphologic mesangial alterations observed in biopsy material are closely reproduced in vitro when mesangial cells grown on an artificial matrix are incubated with monoclonal light chains obtained from the urine of patients with either condition. This article summarizes previously reported data, reports new findings, and focuses on integrating all the available information on the subject. When mesangial cells are incubated with LCDD-LCs, production of ECM proteins (collagen IV, laminin, fibronectin, and tenascin) is increased, with maximum effect at 72 hours post LC treatment. A concomitant decrease in collagenase IV activity further accentuates the accumulation of mesangial matrix. These effects are mediated through transforming growth factor-beta (TGF-beta) activation. In contrast, when mesangial cells are incubated with Am-LCs, a decrease in ECM protein production and a stimulatory effect on collagenase IV is observed, which results in matrix degradation and facilitates amyloid deposition. The decreased TGF-beta documented in the literature in this setting precludes adequate matrix repair. These findings substantiate the morphologic alterations observed in renal biopsy specimens and in the in vitro model. Using this in vitro model, it is then possible to delineate the LC interactions with putative receptors at the mesangial cell surface that regulate mesangial cell pathobiologic responses and mesangial matrix homeostasis." @default.
• W2119320021 created "2016-06-24" @default.
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• W2119320021 date "1999-01-01" @default.
• W2119320021 modified "2023-10-02" @default.
• W2119320021 title "Glomerulopathic Light Chain-Mesangial Cell Interactions Modulate in Vitro Extracellular Matrix Remodeling and Reproduce Mesangiopathic Findings Documented in Vivo" @default.
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• W2119320021 doi "https://doi.org/10.1080/019131299281752" @default.
• W2119320021 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10369104" @default.
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