Faculty Collaboration Database

Antithrombin III prevents progression of chronic kidney disease following experimental ischaemic-reperfusion injury. J Cell Mol Med 2017 Dec;21(12):3506-3514

Date

08/03/2017

Pubmed ID

28767184

Pubmed Central ID

PMC5706518

DOI

10.1111/jcmm.13261

Scopus ID

2-s2.0-85026630186 (requires institutional sign-in at Scopus site)   27 Citations

Abstract

Acute kidney disease (AKI) leads to increased risk of progression to chronic kidney disease (CKD). Antithrombin III (ATIII) is a potent anticoagulant with anti-inflammatory properties, and we previously reported that insufficiencies of ATIII exacerbated renal ischaemia-reperfusion injury (IRI) in rats. In this study, we examined the characteristic of AKI-CKD transition in rats with two distinct AKI models. Based on our observation, left IRI plus right nephrectomy (NX-IRI) was used to determine whether ATIII had therapeutic effects in preventing CKD progression after AKI. It was observed that NX-IRI resulted in significant functional and histological damage at 5 weeks after NX-IRI compared with sham rats, which was mitigated by ATIII administration. Besides, we noticed that ATIII administration significantly reduced NX-IRI-induced interstitial fibrosis. Consistently, renal expression of collagen-1, α-smooth muscle actin and fibronectin were substantial diminished in ATIII-administered rats compared with un-treated NX-IRI rats. Furthermore, the beneficial effects of ATIII were accompanied with decreased M1-like macrophage recruitment and down-regulation of M1-like macrophage-dependent pro-inflammatory cytokines such as tumour necrosis factor α, inducible nitric oxide synthase and interleukin-1β, indicating that ATIII prevented AKI-CKD transition via inhibiting inflammation. Overall, ATIII shows potential as a therapeutic strategy for the prevention of CKD progression after AKI.

Author List

Yin J, Wang F, Kong Y, Wu R, Zhang G, Wang N, Wang L, Lu Z, Liang M

MESH terms used to index this publication - Major topics in bold

Actins
Acute Kidney Injury
Animals
Antithrombin III
Collagen Type I
Disease Models, Animal
Disease Progression
Fibronectins
Fibrosis
Gene Expression Regulation
Interleukin-1beta
Kidney
Macrophages
Male
Nephrectomy
Nitric Oxide Synthase Type II
Rats
Rats, Sprague-Dawley
Reperfusion Injury
Signal Transduction
Tumor Necrosis Factor-alpha