| 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
|
| Resource |
| Mice |
RBRC02370 |
