Inhibitory Effects of STAT3 Transcription Factor by Synthetic Decoy ODNs on Autophagy in Renal Fibrosis

Autor: Hyemin Gu, Mi-Gyeong Gwon, Young-Ah Kim, Hyun-Ju Kim, Kwan-Kyu Park, Seongjae Bae, Hyun Jin Jung, Hyun-Jin An, Jaechan Leem
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Biomedicines, Vol 9, Iss 331, p 331 (2021)
Biomedicines
Volume 9
Issue 4
ISSN: 2227-9059
Popis: Autophagy in the proximal tubules may promote fibrosis by activating tubular cell death, interstitial inflammation, and the production of pro-fibrotic factors. The signal transducer and activator of transcription 3 (STAT3) is activated as a potential transcription factor, which mediates the stimulation of renal fibrosis. We investigated the role of the STAT3 in autophagy and its effect on the prevention of interstitial renal fibrosis. In this study, we use synthesized STAT3 decoy oligonucleotides (ODN), which were injected into the tail veins of unilateral ureteral obstruction (UUO) mice, to explore the regulation of autophagy in UUO-induced renal fibrosis. The expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and collagen were decreased by STAT3 decoy ODN. The autophagy markers microtubule-associated protein light chain 3 (LC3) and fibronectin, were identified through immunofluorescent staining, indicating that they were reduced in the group injected with ODN. The expressions of LC3, Beclin1, p62, and autophagy-related 5–12 (Atg5–12) and hypoxia inducible factor-1α (HIF-1α) were inhibited in the ODN injection group. We determined the inhibitory effect of autophagy in chronic kidney disease and confirmed that STAT3 decoy ODN effectively inhibited autophagy by inhibiting the expression of STAT3 transcription factors in the UUO group.
Databáze: OpenAIRE