Anti-Fibrotic Effect of Synthetic Noncoding Oligodeoxynucleotide for Inhibiting mTOR and STAT3 via the Regulation of Autophagy in an Animal Model of Renal Injury
Renal fibrosis is a common process of various kidney diseases. Autophagy is an important cell biology process to maintain cellular homeostasis. In addition, autophagy is involved in the pathogenesis of various renal disease, including acute kidney injury, glomerular diseases, and renal fibrosis. How...
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MDPI AG
2022-01-01
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| author | Hyun Jin Jung Hyun-Jin An Mi-Gyeong Gwon Hyemin Gu Seongjae Bae Sun-Jae Lee Young-Ah Kim Jaechan Leem Kwan-Kyu Park |
| author_facet | Hyun Jin Jung Hyun-Jin An Mi-Gyeong Gwon Hyemin Gu Seongjae Bae Sun-Jae Lee Young-Ah Kim Jaechan Leem Kwan-Kyu Park |
| author_sort | Hyun Jin Jung |
| collection | DOAJ |
| description | Renal fibrosis is a common process of various kidney diseases. Autophagy is an important cell biology process to maintain cellular homeostasis. In addition, autophagy is involved in the pathogenesis of various renal disease, including acute kidney injury, glomerular diseases, and renal fibrosis. However, the functional role of autophagy in renal fibrosis remains poorly unclear. The mammalian target of rapamycin (mTOR) plays a negative regulatory role in autophagy. Signal transducer and activator of transcription 3 (STAT3) is an important intracellular signaling that may regulate a variety of inflammatory responses. In addition, STAT3 regulates autophagy in various cell types. Thus, we synthesized the mTOR/STAT3 oligodeoxynucleotide (ODN) to regulate the autophagy. The aim of this study was to investigate the beneficial effect of mTOR/STAT3 ODN via the regulation of autophagy appearance on unilateral ureteral obstruction (UUO)-induced renal fibrosis. This study showed that UUO induced inflammation, tubular atrophy, and tubular interstitial fibrosis. However, mTOR/STAT3 ODN suppressed UUO-induced renal fibrosis and inflammation. The autophagy markers have no statistically significant relation, whereas mTOR/STAT3 ODN suppressed the apoptosis in tubular cells. These results suggest the possibility of mTOR/STAT3 ODN for preventing renal fibrosis. However, the role of mTOR/STAT3 ODN on autophagy regulation needs to be further investigated. |
| first_indexed | 2024-03-09T23:28:54Z |
| format | Article |
| id | doaj.art-0779417623ac4fab90d73ff59372b3ee |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T23:28:54Z |
| publishDate | 2022-01-01 |
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| series | Molecules |
| spelling | doaj.art-0779417623ac4fab90d73ff59372b3ee2023-11-23T17:12:08ZengMDPI AGMolecules1420-30492022-01-0127376610.3390/molecules27030766Anti-Fibrotic Effect of Synthetic Noncoding Oligodeoxynucleotide for Inhibiting mTOR and STAT3 via the Regulation of Autophagy in an Animal Model of Renal InjuryHyun Jin Jung0Hyun-Jin An1Mi-Gyeong Gwon2Hyemin Gu3Seongjae Bae4Sun-Jae Lee5Young-Ah Kim6Jaechan Leem7Kwan-Kyu Park8Department of Urology, College of Medicine, Catholic University of Daegu, Daegu 42472, KoreaDepartment of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, KoreaDepartment of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, KoreaDepartment of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, KoreaDepartment of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, KoreaDepartment of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, KoreaDepartment of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, KoreaDepartment of Immunology, College of Medicine, Catholic University of Daegu, Daegu 42472, KoreaDepartment of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, KoreaRenal fibrosis is a common process of various kidney diseases. Autophagy is an important cell biology process to maintain cellular homeostasis. In addition, autophagy is involved in the pathogenesis of various renal disease, including acute kidney injury, glomerular diseases, and renal fibrosis. However, the functional role of autophagy in renal fibrosis remains poorly unclear. The mammalian target of rapamycin (mTOR) plays a negative regulatory role in autophagy. Signal transducer and activator of transcription 3 (STAT3) is an important intracellular signaling that may regulate a variety of inflammatory responses. In addition, STAT3 regulates autophagy in various cell types. Thus, we synthesized the mTOR/STAT3 oligodeoxynucleotide (ODN) to regulate the autophagy. The aim of this study was to investigate the beneficial effect of mTOR/STAT3 ODN via the regulation of autophagy appearance on unilateral ureteral obstruction (UUO)-induced renal fibrosis. This study showed that UUO induced inflammation, tubular atrophy, and tubular interstitial fibrosis. However, mTOR/STAT3 ODN suppressed UUO-induced renal fibrosis and inflammation. The autophagy markers have no statistically significant relation, whereas mTOR/STAT3 ODN suppressed the apoptosis in tubular cells. These results suggest the possibility of mTOR/STAT3 ODN for preventing renal fibrosis. However, the role of mTOR/STAT3 ODN on autophagy regulation needs to be further investigated.https://www.mdpi.com/1420-3049/27/3/766renal fibrosisautophagyoligodeoxynucleotidedecoyantisensemTOR |
| spellingShingle | Hyun Jin Jung Hyun-Jin An Mi-Gyeong Gwon Hyemin Gu Seongjae Bae Sun-Jae Lee Young-Ah Kim Jaechan Leem Kwan-Kyu Park Anti-Fibrotic Effect of Synthetic Noncoding Oligodeoxynucleotide for Inhibiting mTOR and STAT3 via the Regulation of Autophagy in an Animal Model of Renal Injury Molecules renal fibrosis autophagy oligodeoxynucleotide decoy antisense mTOR |
| title | Anti-Fibrotic Effect of Synthetic Noncoding Oligodeoxynucleotide for Inhibiting mTOR and STAT3 via the Regulation of Autophagy in an Animal Model of Renal Injury |
| title_full | Anti-Fibrotic Effect of Synthetic Noncoding Oligodeoxynucleotide for Inhibiting mTOR and STAT3 via the Regulation of Autophagy in an Animal Model of Renal Injury |
| title_fullStr | Anti-Fibrotic Effect of Synthetic Noncoding Oligodeoxynucleotide for Inhibiting mTOR and STAT3 via the Regulation of Autophagy in an Animal Model of Renal Injury |
| title_full_unstemmed | Anti-Fibrotic Effect of Synthetic Noncoding Oligodeoxynucleotide for Inhibiting mTOR and STAT3 via the Regulation of Autophagy in an Animal Model of Renal Injury |
| title_short | Anti-Fibrotic Effect of Synthetic Noncoding Oligodeoxynucleotide for Inhibiting mTOR and STAT3 via the Regulation of Autophagy in an Animal Model of Renal Injury |
| title_sort | anti fibrotic effect of synthetic noncoding oligodeoxynucleotide for inhibiting mtor and stat3 via the regulation of autophagy in an animal model of renal injury |
| topic | renal fibrosis autophagy oligodeoxynucleotide decoy antisense mTOR |
| url | https://www.mdpi.com/1420-3049/27/3/766 |
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