Mesencephalic astrocyte-derived neurotrophic factor as a urine biomarker for endoplasmic reticulum stress-related kidney diseases

Yeawon Kim, Heedoo Lee, Scott R. Manson, Maria Lindahl, Bradley Evans, Jeffrey H. Miner, Fumihiko Urano, Ying Maggie Chen

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Endoplasmic reticulum (ER) stress and disrupted proteostasis contribute to the pathogenesis of a variety of glomerular and tubular diseases. Thus, it is imperative to develop noninvasive biomarkers for detecting ER stress in podocytes or tubular cells in the incipient stage of disease, when a kidney biopsy is not yet clinically indicated. Mesencephalic astrocyte-derived neurotrophic factor (MANF) localizes to the ER lumen and is secreted in response to ER stress in several cell types. Here, using mouse models of human nephrotic syndrome caused by mutant laminin b2 protein-induced podocyte ER stress and AKI triggered by tunicamycin-or ischemiareperfusion-induced tubular ER stress, we examined MANF as a potential urine biomarker for detecting ER stress in podocytes or renal tubular cells. ER stress upregulated MANF expression in podocytes and tubular cells. Notably, urinary MANF excretion concurrent with podocyte or tubular cell ER stress preceded clinical or histologic manifestations of the corresponding disease. Thus, MANF can potentially serve as a urine diagnostic or prognostic biomarker in ER stress-related kidney diseases to help stratify disease risk, predict disease progression, monitor treatment response, and identify subgroups of patients who can be treated with ER stress modulators in a highly targeted manner.

Original languageEnglish
Pages (from-to)2974-2982
Number of pages9
JournalJournal of the American Society of Nephrology
Volume27
Issue number10
DOIs
StatePublished - 2016

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