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SIRT1-dependent dea...
SIRT1-dependent deacetylation of Txnip H3K9ac is critical for exenatide-improved diabetic kidney disease
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- Wang, Mei jun (författare)
- Third Affiliated Hospital of Sun Yat‐sen University,Guangzhou First People's Hospital
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- Cai, Xiang (författare)
- Third Affiliated Hospital of Sun Yat‐sen University
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- Liang, Ri ying (författare)
- Sun Yat-sen University,Third Affiliated Hospital of Sun Yat‐sen University
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- Zhang, En ming (författare)
- Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,Lunds Tekniska Högskola,Diabetes - Islet Patophysiology,Lund University Research Groups,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH
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- Liang, Xiao qi (författare)
- Third Affiliated Hospital of Sun Yat‐sen University
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- Liang, Hua (författare)
- Third Affiliated Hospital of Sun Yat‐sen University
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- Fu, Chang (författare)
- Third Affiliated Hospital of Sun Yat‐sen University
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- Zhou, An dong (författare)
- Third Affiliated Hospital of Sun Yat‐sen University
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- Shi, Yi (författare)
- Third Affiliated Hospital of Sun Yat‐sen University
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- Xu, Fen (författare)
- Third Affiliated Hospital of Sun Yat‐sen University
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- Cai, Meng yin (författare)
- Third Affiliated Hospital of Sun Yat‐sen University
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(creator_code:org_t)
- 2023
- 2023
- Engelska.
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Ingår i: Biomedicine and Pharmacotherapy. - 0753-3322. ; 167
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Glucagon-like peptide 1 receptor agonist exenatide (exendin-4) has potential protective capabilities against diabetic kidney disease (DKD). However, the underlying mechanism has not been fully elucidated. The expression of thioredoxin-interacting protein (Txnip) is upregulated during DKD progression by histone acetylation. Sirtuin 1 (SIRT1) is a deacetylase and is decreased in DKD, which indicates that it may regulate Txnip in this disease. Here, we used whole-body heterozygous Sirt1 knockout (Sirt1+/-) and kidney-specific Sirt1 knockout (KSK) mice to investigate whether SIRT1 regulates Txnip via histone deacetylation in DKD and exenatide-alleviated DKD. Exenatide substantially improved renal pathological damage, decreased the albumin-to-creatinine ratio (ACR), upregulated SIRT1 expression, and downregulated Txnip expression in kidneys of high-fat diet-treated C57BL/6J mice. However, these effects diminished in Sirt1+/- and KSK mice under exenatide treatment. The downregulation of Txnip expression by exendin-4 in high-glucose-treated SV40 MES13 cells was hampered during Sirt1 knockdown. These results demonstrate that kidney SIRT1 is indispensable in exenatide-improved DKD and downregulation of Txnip expression. Exendin-4 mechanistically downregulated Txnip histone 3 lysine 9 acetylation (H3K9ac) in a SIRT1-dependent manner and decreased spliced X-box binding protein 1 (XBP1s) recruitment to the Txnip promoter. These findings provide epigenetic evidence elucidating the specific mechanism for exenatide-mediated DKD alleviation and highlight the importance of Txnip as a promising therapeutic target for DKD.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Diabetic kidney disease
- Exenatide
- Kidney-specific Sirt1 knockout
- Txnip
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Wang, Mei jun
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Cai, Xiang
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Liang, Ri ying
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Zhang, En ming
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Liang, Xiao qi
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Liang, Hua
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visa fler...
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Fu, Chang
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Zhou, An dong
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Shi, Yi
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Xu, Fen
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Cai, Meng yin
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visa färre...
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Lunds universitet