Role of ESAT-6 in renal injury by regulating microRNA-155 expression via TLR4/MyD88 signaling pathway in mice with Mycobacterium tuberculosis infection.

Zhong-Qi Zhou,Nan Zhao,Fu-Yun Sun,Zhong-Wei Ma,Lei Zhang,Yue-Qin Ren,Zhi-Kui Wang,Zhong Wei Ma ,Fu Yun Sun

doi:10.1042/bsr20170021

Zhong-Qi Zhou, Nan Zhao + Show 7 more

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https://doi.org/10.1042/bsr20170021

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Abstract

The study aims to investigate the underlying mechanism involved in the early secretory antigenic target-6 (ESAT-6) in renal injury through regulation of the expression of miR-155 through the oll-like receptor (TLR)-4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway in Mycobacterium tuberculosis (MTB)-infected mice. Sixty C57BL/6 mice with MTB-induced renal injury were randomly assigned into control, MTB, mimic, inhibitor, inhibitor + ESAT6, and inhibitor + ESAT6 + TAK242 groups. Body weight, the ratio of kidney weight to body weight (Kw/Bw), blood urea nitrogen (BUN), and serum creatinine (Scr) of mice were measured. Flow cytometry was used to detect renal activation in mice. Expressions of miR-155 and ESAT6 were detected by quantitative real-time PCR (qRT-PCR), and Western blotting was used to examine the expressions of ESAT6, TLR4, and MyD88. Expressions of tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), and interferon-γ (IFN-γ) were measured by qRT-PCR and ELISA. Compared with the control group, the BUN and Scr levels as well as the expression levels of miR-155, TLR4, MyD88, TNF-α, IL-17, and IFN-γ increased, while Kw/Bw decreased in the MTB and mimic groups. In comparison with the MTB group, the above indexes except Kw/Bw were elevated in the mimic group, but were reduced in the inhibitor group, while the Kw/Bw dropped in the mimic group but increased in the inhibitor group. Compared with the inhibitor group, the Kw/Bw decreased while the rest of the indexes increased in the inhibitor + ESAT6 group. ESAT6 may induce renal injury by promoting miR-155 expression through the TLR-4/MyD88 signaling pathway in MTB-infected mice.

Highlights

Renal injury, known as kidney injury, is featured by the progressive degradation in relation to renal function
In comparison with the Mycobacterium tuberculosis (MTB) group, the body weight reduced in the mimic group but increased in the inhibitor group, and the kidney weight and kidney weight to body weight (Kw/Bw) increased in the mimic group but decreased in the inhibitor group
Compared with the inhibitor group, the body weight decreased while kidney weight and Kw/Bw increased in the inhibitor + ESAT6 group, and there was no significant difference between the inhibitor + ESAT6 + TAK242 and the inhibitor group (P>0.05)

Summary

Introduction

Known as kidney injury, is featured by the progressive degradation in relation to renal function. The decline of glomerular filtration rate (GFR) that accompanies renal injury results in the deposition of urea and various other chemicals into the blood [1]. 245000 cases of renal injury occur worldwide each year. Renal injuries have been reported to be the most frequently occurring genitourinary injury [2,3]. The risk factors of renal injury include age, blood glucose, and patients with reduced baseline renal function tend to develop renal injury [5]. The most common treatment for renal injury is renal replacement therapy and cell-based therapy, correction of uremia-associated factors and protein restriction are therapeutic options [6,7].

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