SIK2 protects against renal tubular injury and the progression of diabetic kidney disease

Liu, Bingyao; Zhang, Linlin; Yang, Hang; Chen, Xinyu; Wang, Cong-Yi; Liao, Xiaoyu

doi:10.1016/j.trsl.2022.08.012

Cited by 6 publications

(3 citation statements)

References 86 publications

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“…Apoptosis is a tightly controlled process that is critical for cell growth and development [29,30]. Growing evidence supports the idea that tubular epithelial cell apoptosis plays a crucial role in DN pathogenesis [31,32]. Under normal conditions, an equilibrium between autophagy and apoptosis is maintained in the body [29].…”

Section: Discussionmentioning

confidence: 97%

Colquhounia Root Tablet Promotes Autophagy and Inhibits Apoptosis in Diabetic Nephropathy by Suppressing CD36 Expression In Vivo and In Vitro

Han

Wang

et al. 2023

Journal of Diabetes Research

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Background/Aims. Accumulating clinical evidence suggests that Colquhounia root tablet (CRT) has the potential to alleviate diabetic nephropathy (DN); however, the exact mechanism of action remains unclear. Here, we report the effects of CRT administration on apoptosis and autophagy and attempt to elucidate the underlying mechanisms in vivo and in vitro. Methods. Rat models of DN were established using streptozotocin (STZ). The primary metabolic parameters were assessed. The pathological changes of the rat kidney were investigated, and RNA sequencing was performed for each group. Renal tissue apoptosis was detected using the TUNEL assay. In rats and high glucose- (Hg-) induced HK-2 cells, RT-qPCR and western blot were used to analyze the expression of related genes and proteins. Hg medium was used to establish the diabetic kidney environment. The CCK-8 assay and flow cytometry were used to assess cell viability and apoptosis, respectively. Transmission electron microscopy was used to evaluate autophagy in vitro. Results. CRT treatment significantly reduced albuminuria and renal tissue damage in DN rats. Furthermore, CRT administration inhibited apoptosis and promoted autophagy in DN rat kidney tissues. CRT downregulated CD36 expression and activated the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in DN rat kidney tissues. CRT intervention inhibited Hg-induced apoptosis and reversed autophagy in HK-2 cells. Moreover, overexpression of CD36 suppressed the beneficial effects of CRT. Conclusions. Our study is the first to report that CRT inhibited apoptosis and promoted autophagy in vivo and in vitro, which was achieved by reducing CD36 expression and activating the AMPK pathway. Therefore, CRT may be an effective drug to treat DN.

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Section: Discussionmentioning

confidence: 97%

Colquhounia Root Tablet Promotes Autophagy and Inhibits Apoptosis in Diabetic Nephropathy by Suppressing CD36 Expression In Vivo and In Vitro

Han

Wang

et al. 2023

Journal of Diabetes Research

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“…In a more recent work, Liu et al demonstrated that the restoration of the activity of the salt-inducible kinase SIK2 is a promising therapy for diabetic patients with interstitial fibrotic kidney disease, since the underlying molecular mechanisms involve the EP300dependent SIK2 inactivity in renal tubules of patients and in vivo models using vancomycininduced kidney disease in murine experiments [54]. Consistently, previous groups linked the SIK2-mediated inhibition of EP300 with a phosphorylation-based modification on Ser89, as it has been recently validated by ex vivo approaches [7].…”

Section: Renal Fibrosismentioning

confidence: 99%

EP300 as a Molecular Integrator of Fibrotic Transcriptional Programs

Rubio,

Molina-Herrera,

Pérez-González

et al. 2023

IJMS

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Fibrosis is a condition characterized by the excessive accumulation of extracellular matrix proteins in tissues, leading to organ dysfunction and failure. Recent studies have identified EP300, a histone acetyltransferase, as a crucial regulator of the epigenetic changes that contribute to fibrosis. In fact, EP300-mediated acetylation of histones alters global chromatin structure and gene expression, promoting the development and progression of fibrosis. Here, we review the role of EP300-mediated epigenetic regulation in multi-organ fibrosis and its potential as a therapeutic target. We discuss the preclinical evidence that suggests that EP300 inhibition can attenuate fibrosis-related molecular processes, including extracellular matrix deposition, inflammation, and epithelial-to-mesenchymal transition. We also highlight the contributions of small molecule inhibitors and gene therapy approaches targeting EP300 as novel therapies against fibrosis.

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“…The pathological changes of DKD contain basement membrane thickening, mesangial cell hypertrophy, podocyte loss and apoptosis, tubulointerstitial brosis [2] . Particularly, podocytes apoptosis and renal tubular epithelial cell damage play an important role in the pathogenesis of DKD [3][4][5] . Due to requirement of high-energy and aerobic metabolism, renal tubules are more susceptible to the metabolic disturbances, leading to in ammation and brosis associated with DKD [6] .…”

Section: Introductionmentioning

confidence: 99%

Expression profile of urinary exosomal miRNAs in patients with diabetic kidney disease and their associated with kidney damage

Li,

Han,

Wang

et al. 2024

Preprint

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Purpose Diabetic kidney disease (DKD) is the primary cause of end-stage renal disease. The aim of study is to seek noninvasive biomarkers for DKD at early stage or a target for the treatment of DKD through analysis of the urinary exosomal miRNAs expression profiles in DKD patients. Methods The urinary exosomes were isolated from type 2 diabetes (T2DM) patients with DKD confirmed by renal biopsy (DKD-Exo). Treatment of human podocytes and renal tubular epithelial cells (TECs) with DKD-Exo to observe the effects of DKD-Exo on podocyte apoptosis and epithelial-mesenchymal transition (EMT) of TECs. The urinary exosomal miRNAs expression profiles were detected using miRNA sequencing, and differentially expressed miRNAs were verified by real-time quantitative PCR. Target genes of these miRNAs and relevant pathways in DKD were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Results DKD-Exo induced the apoptosis of podocytes and EMT of TECs. A total of 40 differentially downregulated miRNAs were found, 17 of all were named and 23 were newly discovered, some differentially expressed miRNAs in DKD patients were reported for the first time. GO and KEGG pathway analysis suggest that these target genes were related to biological processes, molecular function and cellular component, and involved in 135 pathways. Conclusion Our study implies that the urinary DKD-Exo could deliver biological information to podocytes or TECs, which play an important role in pathogenesis of DKD.

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SIK2 protects against renal tubular injury and the progression of diabetic kidney disease

Cited by 6 publications

References 86 publications

Colquhounia Root Tablet Promotes Autophagy and Inhibits Apoptosis in Diabetic Nephropathy by Suppressing CD36 Expression In Vivo and In Vitro

Colquhounia Root Tablet Promotes Autophagy and Inhibits Apoptosis in Diabetic Nephropathy by Suppressing CD36 Expression In Vivo and In Vitro

EP300 as a Molecular Integrator of Fibrotic Transcriptional Programs

Expression profile of urinary exosomal miRNAs in patients with diabetic kidney disease and their associated with kidney damage

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