Protective Mechanism of Apigenin in Diabetic Nephropathy is Related to Its Regulation of MiR-423-5P-USF2 Axis

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2021 May 21

PMID 34017372

Citations 8

Authors

Yi Hou

Yan Zhang

Sitong Lin

Yue Yu

Liu Yang

Lei Li

Wenxiang Wang

Affiliations

Soon will be listed here.

Abstract

Apigenin (APG), a natural flavonoid with anti-inflammatory and anti-fibrosis properties, has been shown to play a protective role in diabetic nephropathy (DN), but their molecular protection mechanism for miRNA has not been elucidated in detail. This study was designed to focus on exploring its protective role in DN and whether miR-423-5p-upstream stimulating factor 2 (USF2) axis was involved in its protective mechanism. The in vivo model of rat was induced by streptozotocin (STZ) and the in vitro model of renal tubular epithelial cell (RTEC) was induced by high glucose (HG). Our in vivo study revealed that APG had different protective effects on inflammation, renal fibrosis and epithelial mesenchymal transition (EMT) in DN rats, which is mainly reflected in that the inflammatory factors (IL-6, IFN-γ, TNF-α) were obviously down-regulated, the renal fibrosis markers (IV-C, FN, Col I) were significantly inhibited, the E-cadherin (EMT factors) was significantly up-regulated, while the vimentin and α-SMA (EMT factors) were significantly down-regulated, and the renal function indexes (serum Cr, BUN) were significantly improved. In terms of mechanism, the protective effect of APG was related to the regulation of the expression of miR-423-5p-USF2 axis, and there was a targeted relationship between miR-423-5p and USF2. Down-regulating miR-423-5p or up-regulating USF2 could significantly aggravate the disease progression of in vitro model and eliminate DN resistance under APG intervention. The above results revealed that the protective role of APG on DN was mediated by miR-423-5p-USF2 axis.

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