Premium
Overexpression of Elabela Transgene Ameliorates UUO‐Induced Renal Fibrosis through Suppressing TGF‐β in Sparague‐Dawley Rats
Author(s) -
Wu Chunying,
Zhu Yeyan,
Li Haonan,
Wang Lei,
Zhu Qing
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.802.66
Subject(s) - transgene , fibronectin , kidney , fibrosis , messenger rna , downregulation and upregulation , transforming growth factor , receptor , transfection , medicine , endocrinology , biology , microbiology and biotechnology , gene , extracellular matrix , biochemistry
Elabela (ELA) is a newly discovered endogenous ligand of APJ receptor, which is widely distributed in various tissues and organs including kidney. Accumulated evidences demonstrate that ELA plays a critical role in the regulation of renal physiology and pathophysiology. Our preliminary data showed that ELA expression was significantly inhibited in the kidney of unilateral ureteral obstruction (UUO) rats. However it remains unknown whether ELA has renoprotective effects in UUO model. The present study tested the hypothesis that overexpression of ELA transgenes protect against renal fibrosis in UUO rats. Male Sprague‐ Dawley rats (200–250g body weight) were subjected to UUO surgery and plasmids expressing ELA transgenes or control vectors were transfected into the obstructed kidneys via renal arteries. After 7 days, the rats were scarified and the kidneys were collected for analysis. The ELA mRNA levels were decreased by 70% in UUO rats compared to that of the control rats, which were significantly increased by 2‐fold in the UUO+ELA plasmids‐treated rats, suggesting successful overexpression of ELA in the kidney via transfection of ELA overexpression plasmid. Siris red staining results showed that collagen accumulation was increased in the UUO rats, which was dramatically suppressed in UUO+ELA plasmids‐treated animals. The mRNA levels of Collagen I, Fibronectin and α‐SMA were all elevated in the UUO group and were notably attenuated in the UUO+ELA plasmids‐treated group. Furthermore we examined the expression of TGF‐β, a central mediator of renal fibrosis and the results showed that the mRNA and protein levels of TGF‐β were upregulated in UUO rats but greatly decreased in UUO+ELA plasmids‐treated rats. These results suggest that the impaired activation of ELA in the kidney may represent a novel mechanism for renal fibrosis under pathological condition and that correction of this impairment may serve as a novel therapeutic approach for the treatment of chronic renal fibrotic diseases. Support or Funding Information This work was supported by grants from the National Natural Science Foundation of China: No. 81600322 and No. 81770707 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .