Autophagy Exacerbates the Lysosomal Dysfunction of Late-Stage Atherosclerosis

Jerome, W.G.; Dyke, C.D. Netherland-Van; Romer, Carrie

doi:10.1017/s1431927613003061

Cited by 1 publication

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“…In correlation with the increased accumulation of giant lysosomes, the augmented expression of lysosomal-associated membrane protein 1 was also found in AGE-BSA-treated cells, indicating an increased number and size of lysosomes, a hallmark of lysosomal dysfunction (Fig. 6C and D) (31,32). Furthermore, AGE-BSA treatment for 48 h caused increased MVB formation, as indicated by the augmented cellular expression of the endosomal sorting complex required for transport-associated proteins TSG101 ( Fig.…”

Section: Age-bsa Induces Lysosomal Dysfunction and Causes Increased Mmentioning

confidence: 72%

Exocytosis-Mediated Urinary Full-Length Megalin Excretion Is Linked With the Pathogenesis of Diabetic Nephropathy

Kudoh

Hosojima

et al. 2017

Diabetes

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Efficient biomarkers for diabetic nephropathy (DN) have not been established. Using ELISA, we found previously that urinary levels of full-length megalin (C-megalin), a multiligand endocytic receptor in proximal tubules, was positively correlated with DN progression in patients with type 2 diabetes mellitus (T2DM). Here, we found that urinary extracellular vesicle (UEV) excretion and C-megalin content in UEVs or in their exosomal fraction increased along with the progression of the albuminuric stages in patients with T2DM. Cultured immortalized rat proximal tubule cells (IRPTCs) treated with fatty acid-free BSA or advanced glycation end product-modified BSA (AGE-BSA), endocytic ligands of megalin, increased EV excretion, and their C-megalin content. C-megalin excretion from IRPTCs via extracellular vesicles was significantly blocked by an exosome-specific inhibitor, GW4869, indicating that this excretion is mainly exocytosis-mediated. AGE-BSA treatment of IRPTCs caused apparent lysosomal dysfunction, which stimulated multivesicular body formation, resulting in increased exosomal C-megalin excretion. In a high-fat diet-induced, megalin-mediated kidney injury model in mice, urinary C-megalin excretion also increased via UEVs. Collectively, exocytosis-mediated urinary C-megalin excretion is associated with the development and progression of DN in patients with T2DM, particularly due to megalin-mediated lysosomal dysfunction in proximal tubules, and hence it could be a candidate biomarker linked with DN pathogenesis.

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Section: Age-bsa Induces Lysosomal Dysfunction and Causes Increased Mmentioning

confidence: 72%

Exocytosis-Mediated Urinary Full-Length Megalin Excretion Is Linked With the Pathogenesis of Diabetic Nephropathy

Kudoh

Hosojima

et al. 2017

Diabetes

View full text Add to dashboard Cite

show abstract

Autophagy Exacerbates the Lysosomal Dysfunction of Late-Stage Atherosclerosis

Abstract: Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.

Cited by 1 publication

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Exocytosis-Mediated Urinary Full-Length Megalin Excretion Is Linked With the Pathogenesis of Diabetic Nephropathy

Exocytosis-Mediated Urinary Full-Length Megalin Excretion Is Linked With the Pathogenesis of Diabetic Nephropathy

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