Inhibitory Effects of STAT3 Transcription Factor by Synthetic Decoy ODNs on Autophagy in Renal Fibrosis
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 stimulat...
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MDPI AG
2021-03-01
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| Online Access: | https://www.mdpi.com/2227-9059/9/4/331 |
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| author | Young-Ah Kim Hyun-Ju Kim Mi-Gyeong Gwon Hyemin Gu Hyun-Jin An Seongjae Bae Jaechan Leem Hyun Jin Jung Kwan-Kyu Park |
| author_facet | Young-Ah Kim Hyun-Ju Kim Mi-Gyeong Gwon Hyemin Gu Hyun-Jin An Seongjae Bae Jaechan Leem Hyun Jin Jung Kwan-Kyu Park |
| author_sort | Young-Ah Kim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T12:54:16Z |
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| language | English |
| last_indexed | 2024-03-10T12:54:16Z |
| publishDate | 2021-03-01 |
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| series | Biomedicines |
| spelling | doaj.art-7c9a1cc429ea4cb9abf73632804c6a7c2023-11-21T12:01:12ZengMDPI AGBiomedicines2227-90592021-03-019433110.3390/biomedicines9040331Inhibitory Effects of STAT3 Transcription Factor by Synthetic Decoy ODNs on Autophagy in Renal FibrosisYoung-Ah Kim0Hyun-Ju Kim1Mi-Gyeong Gwon2Hyemin Gu3Hyun-Jin An4Seongjae Bae5Jaechan Leem6Hyun Jin Jung7Kwan-Kyu Park8Department of Pathology, School of Medicine, Catholic University of Daegu, Daegu 42472, KoreaDepartment of Pathology, School of Medicine, Catholic University of Daegu, Daegu 42472, KoreaDepartment of Pathology, School of Medicine, Catholic University of Daegu, Daegu 42472, KoreaDepartment of Pathology, School of Medicine, Catholic University of Daegu, Daegu 42472, KoreaDepartment of Pathology, School of Medicine, Catholic University of Daegu, Daegu 42472, KoreaDepartment of Pathology, School of Medicine, Catholic University of Daegu, Daegu 42472, KoreaDepartment of Immunology, School of Medicine, Catholic University of Daegu, Daegu 42472, KoreaDepartment of Urology, School of Medicine, Catholic University of Daegu, Daegu 42472, KoreaDepartment of Pathology, School of Medicine, Catholic University of Daegu, Daegu 42472, KoreaAutophagy 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.https://www.mdpi.com/2227-9059/9/4/331STAT3decoy ODNsautophagyrenal fibrosisUUO |
| spellingShingle | Young-Ah Kim Hyun-Ju Kim Mi-Gyeong Gwon Hyemin Gu Hyun-Jin An Seongjae Bae Jaechan Leem Hyun Jin Jung Kwan-Kyu Park Inhibitory Effects of STAT3 Transcription Factor by Synthetic Decoy ODNs on Autophagy in Renal Fibrosis Biomedicines STAT3 decoy ODNs autophagy renal fibrosis UUO |
| title | Inhibitory Effects of STAT3 Transcription Factor by Synthetic Decoy ODNs on Autophagy in Renal Fibrosis |
| title_full | Inhibitory Effects of STAT3 Transcription Factor by Synthetic Decoy ODNs on Autophagy in Renal Fibrosis |
| title_fullStr | Inhibitory Effects of STAT3 Transcription Factor by Synthetic Decoy ODNs on Autophagy in Renal Fibrosis |
| title_full_unstemmed | Inhibitory Effects of STAT3 Transcription Factor by Synthetic Decoy ODNs on Autophagy in Renal Fibrosis |
| title_short | Inhibitory Effects of STAT3 Transcription Factor by Synthetic Decoy ODNs on Autophagy in Renal Fibrosis |
| title_sort | inhibitory effects of stat3 transcription factor by synthetic decoy odns on autophagy in renal fibrosis |
| topic | STAT3 decoy ODNs autophagy renal fibrosis UUO |
| url | https://www.mdpi.com/2227-9059/9/4/331 |
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