RRC ID 63377
Author Murakoshi M, Gohda T, Adachi E, Ichikawa S, Hagiwara S, Suzuki Y.
Title Differential organ-specific inflammatory response to progranulin in high-fat diet-fed mice.
Journal Sci Rep
Abstract Progranulin (PGRN) has been reported to bind tumor necrosis factor (TNF) receptor and to inhibit TNFα signaling. We evaluated the effect of augmentation of TNFα signaling by PGRN deficiency on the progression of kidney injury. Eight-week-old PGRN knockout (KO) and wild-type (WT) mice were fed a standard diet or high-fat diet (HFD) for 12 weeks. Albuminuria, markers of tubular damage, and renal mRNA levels of inflammatory cytokines were higher in HFD-fed KO (KO-HFD) mice than in HFD-fed WT (WT-HFD) mice. Body weight, vacuolization in proximal tubules, and systemic and adipose tissue inflammatory markers were lower in the KO-HFD mice than in the WT-HFD mice. The renal megalin expression was lower in the KO mice than in the WT mice regardless of the diet type. The megalin expression was also reduced in mouse proximal tubule epithelial cells stimulated with TNFα and in those with PGRN knockdown by small interfering RNA in vitro. PGRN deficiency was associated with both exacerbated renal inflammation and decreased systemic inflammation, including that in the adipose tissue of mice with HFD-induced obesity. Improved tubular vacuolization in the KO-HFD mice might partially be explained by the decreased expression of megalin in proximal tubules.
Volume 11(1)
Pages 1194
Published 2021-1-13
DOI 10.1038/s41598-020-80940-8
PII 10.1038/s41598-020-80940-8
PMID 33441916
PMC PMC7806827
MeSH Adipose Tissue / metabolism Animals Body Weight / physiology Cells, Cultured Diet, High-Fat / adverse effects Inflammation / metabolism* Insulin Resistance / physiology Kidney Tubules, Proximal / metabolism Low Density Lipoprotein Receptor-Related Protein-2 / metabolism Mice Mice, Inbred C57BL Mice, Knockout Obesity / metabolism Progranulins / metabolism* Signal Transduction / physiology Tumor Necrosis Factor-alpha / metabolism
IF 3.998
Mice RBRC02370