In:
Food & Function, Royal Society of Chemistry (RSC)
Abstract:
As one of the most significant pathological changes of diabetic nephropathy (DN), tubulointerstitial fibrosis (TIF) had a closely relationship with tubulointerstitial inflammation (TI), and the occurrence of TI could be resulted from the disrupted tight junction (TJ) of renal tubular epithelial cells (RTECs). Studies had demonstrated that sodium butyrate (NaB), a typical short chain fatty acid (SCFA), played an important regulatory role in intestinal TJs and inflammation. In this study, our in vivo and in vitro results showed that accompanying with TI, renal tubular TJs were gradually disrupted in the process of DN-related TIF. In HG and LPS co-cultured HK-2 cells and db/db mice, NaB treatment regained TJs of RTECs via sphingosine 1-phosphate receptor-1 (S1PR1)/AMPK signaling pathway, leading to the relieved inflammation. Small interfering RNA of S1PR1, S1PR1 antagonist W146 and agonist SEW2871, and AMPK agonist AICAR were all used to further confirmed the essential role of S1PR1/AMPK signaling pathway in NaB’ TJs protection of RTECs in vitro. Finally, NaB administration not only improved renal function and TIF, but also relieved TI of db/db mice. These findings suggested that NaB might be a potential adjuvant treatment strategy for DN-associated TIF, and this protective effect was linked to TJs modulation of RTECs via S1PR1/AMPK signaling pathway, causing the improvement of TI.
Type of Medium:
Online Resource
ISSN:
2042-6496
,
2042-650X
Language:
English
Publisher:
Royal Society of Chemistry (RSC)
Publication Date:
2022
detail.hit.zdb_id:
2578152-2
SSG:
21
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