ISSN: 1838-7640Theranostics
Global reach, higher impact
Theranostics 2020; 10(16):7319-7334. doi:10.7150/thno.44054 This issue Cite
Research Paper
Sulforaphane elicts dual therapeutic effects on Renal Inflammatory Injury and crystal deposition in Calcium Oxalate Nephrocalcinosis
1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
2. Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.
3. Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
4. Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
5. Department of Urology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
*These authors contributed equally to this work.
Citation:
Liu H, Yang X, Tang K, Ye T, Duan C, Lv P, Yan L, Wu X, Chen Z, Liu J, Deng Y, Zeng G, Xing J, Ye Z, Xu H. Sulforaphane elicts dual therapeutic effects on Renal Inflammatory Injury and crystal deposition in Calcium Oxalate Nephrocalcinosis. Theranostics 2020; 10(16):7319-7334. doi:10.7150/thno.44054. https://www.thno.org/v10p7319.htm
Other stylesAbstract
Intrarenal calcium oxalate (CaOx) crystals induce renal tubular epithelial cells (TECs) injury and inflammation, which involve Toll-like receptor 4 (TLR4)/interferon regulatory factor 1 (IRF1) signaling. Additionally, infiltrating macrophages (Mϕs) might influence intrarenal CaOx crystals and CaOx-induced renal injury. Although the roles of nuclear factor erythroid 2-related factor 2 (Nrf2) in regulating inflammation and macrophage polarization are well characterized, its potential mechanisms in regulating CaOx nephrocalcinosis remain undefined.
Methods: We used a Gene Expression Omnibus dataset to analyze gene-expression profiles. Luciferase reporter, western blot, quantitative polymerase chain reaction, immunofluorescence staining, fluorescence in situ hybridization, positron emission tomography computed tomography imaging, flow cytometry, and chromatin immunoprecipitation assays were employed to study the mechanism of miR-93-TLR4/IRF1 regulation by Nrf2. Anti-inflammatory activity and regulation of macrophage polarization by Nrf2 were investigated in vitro and in vivo.
Results: We found that stone-mediated kidney inflammation significantly affected stone growth, and that sulforaphane attenuated CaOx nephrocalcinosis-induced kidney injury and renal CaOx crystals deposition. Additionally, Nrf2 levels significantly increased and negatively correlated with TLR4 and IRF1 levels in a mouse model of CaOx nephrocalcinosis following sulforaphane treatment. Moreover, Nrf2 suppressed TLR4 and IRF1 levels and decreased M1-macrophage polarization which induced by supernatants from COM-stimulated TECs in vitro. In terms of mechanism, transcription factor analyses, microRNA microarray, and chromatin immunoprecipitation assays showed that Nrf2 exhibited positive transcriptional activation of miR-93-5p. In addition, Luciferase reporter, qRT-PCR, and western blot validated that miR-93-5p targets TLR4 and IRF1 mRNA. Furthermore, suppressed miR-93-5p expression partially reversed Nrf2-dependent TLR4/IRF1 downregulation.
Conclusions: The results suggested that sulforaphane might promote M2Mϕ polarization and inhibit CaOx nephrocalcinosis-induced inflammatory injury to renal tubular epithelial cells via the Nrf2-miR-93-TLR4/IRF1 pathway in vitro and in vivo.
Keywords: Sulforaphane, Nrf2, TLR4, IRF1, Macrophage
Citation styles
APA
Liu, H., Yang, X., Tang, K., Ye, T., Duan, C., Lv, P., Yan, L., Wu, X., Chen, Z., Liu, J., Deng, Y., Zeng, G., Xing, J., Ye, Z., Xu, H. (2020). Sulforaphane elicts dual therapeutic effects on Renal Inflammatory Injury and crystal deposition in Calcium Oxalate Nephrocalcinosis. Theranostics, 10(16), 7319-7334. https://doi.org/10.7150/thno.44054.
ACS
Liu, H.; Yang, X.; Tang, K.; Ye, T.; Duan, C.; Lv, P.; Yan, L.; Wu, X.; Chen, Z.; Liu, J.; Deng, Y.; Zeng, G.; Xing, J.; Ye, Z.; Xu, H. Sulforaphane elicts dual therapeutic effects on Renal Inflammatory Injury and crystal deposition in Calcium Oxalate Nephrocalcinosis. Theranostics 2020, 10 (16), 7319-7334. DOI: 10.7150/thno.44054.
NLM
Liu H, Yang X, Tang K, Ye T, Duan C, Lv P, Yan L, Wu X, Chen Z, Liu J, Deng Y, Zeng G, Xing J, Ye Z, Xu H. Sulforaphane elicts dual therapeutic effects on Renal Inflammatory Injury and crystal deposition in Calcium Oxalate Nephrocalcinosis. Theranostics 2020; 10(16):7319-7334. doi:10.7150/thno.44054. https://www.thno.org/v10p7319.htm
CSE
Liu H, Yang X, Tang K, Ye T, Duan C, Lv P, Yan L, Wu X, Chen Z, Liu J, Deng Y, Zeng G, Xing J, Ye Z, Xu H. 2020. Sulforaphane elicts dual therapeutic effects on Renal Inflammatory Injury and crystal deposition in Calcium Oxalate Nephrocalcinosis. Theranostics. 10(16):7319-7334.
This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.