| RRC ID |
88392
|
| 著者 |
Xu S, Luo W, Xu X, Qian Y, Xu Z, Yu W, Shan X, Guan X, Lum H, Zhou H, Wang Y.
|
| タイトル |
MD2 blockade prevents oxLDL-induced renal epithelial cell injury and protects against high-fat-diet-induced kidney dysfunction.
|
| ジャーナル |
J Nutr Biochem
|
| Abstract |
There is a strong epidemiological link between obesity, a growing worldwide concern, and kidney disease. Emerging evidence indicates that the pathogenic basis of obesity-related kidney disease may be attributed to Toll-like receptor 4 (TLR4) of the innate immune system. We hypothesized that renal epithelial cell injury in response to oxidized low-density lipoprotein (oxLDL) requires myeloid differentiation factor 2 (MD2), a co-receptor of TLR4. Moreover, we also hypothesized that renal dysfunction is MD2-dependent in the high-fat diet (HFD) mouse model. Results indicated that the MD2 selective inhibitor (L6H21) abrogated the oxLDL-induced formation of MD2-TLR4 dimerization in the renal proximal tubular epithelial cell line NRK-52E. Further, MD2 blockade in NRK-52E cells using siRNA target sequences or L6H21 prevented oxLDL-induced cell injury as indicated by expression of profibrotic molecules, autophagic activity and apoptosis. Similarly, TLR4 knockdown in NRK-52E cells using siRNA target sequences prevented oxLDL-induced cell injury. In the HFD mouse model, MD2 knockout protected against development of kidney dysfunction and renal tissue injury, corroborating the observations observed in NRK-52E cells. Thus, the oxLDL-induced renal tubular epithelial cell profibrotic responses, autophagy and apoptosis were dependent on MD2, as were the renal dysfunction and tissue impairment in HFD mice. These are new findings indicating that the MD2-TLR4 immune signaling complex is a critical pathogenic factor in the development of kidney disease related to obesity or metabolic syndrome.
|
| 巻・号 |
70
|
| ページ |
47-55
|
| 公開日 |
2019-8-1
|
| DOI |
10.1016/j.jnutbio.2019.04.003
|
| PII |
S0955-2863(18)31063-5
|
| PMID |
31151053
|
| MeSH |
Animals
Apoptosis
Autophagy
Cell Line
Diet, High-Fat*
Epithelial Cells / metabolism
Epithelial Cells / pathology*
Immune System
Immunity, Innate
Kidney / metabolism*
Kidney / physiopathology
Lipoproteins, LDL / metabolism*
Lymphocyte Antigen 96 / antagonists & inhibitors*
Lymphocyte Antigen 96 / metabolism
Magnetic Resonance Spectroscopy
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Protein Multimerization
RNA, Small Interfering / metabolism
Rats
Toll-Like Receptor 4 / metabolism*
|
| IF |
4.873
|
| リソース情報 |
| 実験動物マウス |
RBRC02388 |
