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Trichosanthes kirilowii lectin alleviates diabetic nephropathy by inhibiting the LOX1/NF-κB/caspase-9 signaling pathway

Trichosanthes kirilowii lectin (TKL) has been reported to exert hypoglycemic effects in alloxan-induced diabetic mice. However, there is no evidence showing that it helps to prevent diabetic nephropathy (DN). We used a high glucose (HG)-induced HK-2 cell model and a streptozocin (STZ)-induced Wistar...

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Detalles Bibliográficos
Autores principales: Lu, Jiandong, Peng, Jinting, Xiang, Min, He, Liangping, Wang, Dongcai, Xiong, Guoliang, Li, Shunmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127671/
https://www.ncbi.nlm.nih.gov/pubmed/30038056
http://dx.doi.org/10.1042/BSR20180071
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author Lu, Jiandong
Peng, Jinting
Xiang, Min
He, Liangping
Wang, Dongcai
Xiong, Guoliang
Li, Shunmin
author_facet Lu, Jiandong
Peng, Jinting
Xiang, Min
He, Liangping
Wang, Dongcai
Xiong, Guoliang
Li, Shunmin
author_sort Lu, Jiandong
collection PubMed
description Trichosanthes kirilowii lectin (TKL) has been reported to exert hypoglycemic effects in alloxan-induced diabetic mice. However, there is no evidence showing that it helps to prevent diabetic nephropathy (DN). We used a high glucose (HG)-induced HK-2 cell model and a streptozocin (STZ)-induced Wistar rat model to investigate the effects of TKL on DN, as well as the mechanisms for those effects. Our results showed that TKL significantly increased the viability of HG-treated HK-2 cells and inhibited cell apoptosis. In vivo experiments demonstrated that TKL attenuated STZ-induced histopathological damage and the inflammatory response in rat kidney tissues. Pre-treatment of HK-2 cells or STZ-treated rats with polyinosinic acid (Poly IC), an inhibitor of lectin-like oxLDL receptor 1 (LOX1), blocked the protective effect of TKL against HG- or STZ-induced damage to kidney tissue, indicating that TKL might exert its effect via LOX1-mediated endocytosis. Additional results suggested that TKL inhibits the phosphorylation of IκB kinase β (IKKβ) and the nuclear factor-κB (NF-κB) inhibitor protein (IκBα), and thereby reduces the nuclear translocation of NF-κB (p65). ChIP assay data indicated that TKL markedly inhibits the binding of p65 to the CASP9 gene in HG-treated HK-2 cells, subsequently suppressing transcription of the CASP9 gene. In the dual-luciferase reporter assay, TKL significantly inhibited luciferase activity in cells co-transfected with p65 and a wild-type capase-9 construct instead of mutated caspase-9 constructs. Taken together, our results show that TKL helps to protect against DN by inhibiting the LOX1/NF-κB/caspase-9 signaling pathway, suggesting TKL as a promising agent for treating DN.
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spelling pubmed-61276712018-09-11 Trichosanthes kirilowii lectin alleviates diabetic nephropathy by inhibiting the LOX1/NF-κB/caspase-9 signaling pathway Lu, Jiandong Peng, Jinting Xiang, Min He, Liangping Wang, Dongcai Xiong, Guoliang Li, Shunmin Biosci Rep Research Articles Trichosanthes kirilowii lectin (TKL) has been reported to exert hypoglycemic effects in alloxan-induced diabetic mice. However, there is no evidence showing that it helps to prevent diabetic nephropathy (DN). We used a high glucose (HG)-induced HK-2 cell model and a streptozocin (STZ)-induced Wistar rat model to investigate the effects of TKL on DN, as well as the mechanisms for those effects. Our results showed that TKL significantly increased the viability of HG-treated HK-2 cells and inhibited cell apoptosis. In vivo experiments demonstrated that TKL attenuated STZ-induced histopathological damage and the inflammatory response in rat kidney tissues. Pre-treatment of HK-2 cells or STZ-treated rats with polyinosinic acid (Poly IC), an inhibitor of lectin-like oxLDL receptor 1 (LOX1), blocked the protective effect of TKL against HG- or STZ-induced damage to kidney tissue, indicating that TKL might exert its effect via LOX1-mediated endocytosis. Additional results suggested that TKL inhibits the phosphorylation of IκB kinase β (IKKβ) and the nuclear factor-κB (NF-κB) inhibitor protein (IκBα), and thereby reduces the nuclear translocation of NF-κB (p65). ChIP assay data indicated that TKL markedly inhibits the binding of p65 to the CASP9 gene in HG-treated HK-2 cells, subsequently suppressing transcription of the CASP9 gene. In the dual-luciferase reporter assay, TKL significantly inhibited luciferase activity in cells co-transfected with p65 and a wild-type capase-9 construct instead of mutated caspase-9 constructs. Taken together, our results show that TKL helps to protect against DN by inhibiting the LOX1/NF-κB/caspase-9 signaling pathway, suggesting TKL as a promising agent for treating DN. Portland Press Ltd. 2018-09-07 /pmc/articles/PMC6127671/ /pubmed/30038056 http://dx.doi.org/10.1042/BSR20180071 Text en © 2018 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Lu, Jiandong
Peng, Jinting
Xiang, Min
He, Liangping
Wang, Dongcai
Xiong, Guoliang
Li, Shunmin
Trichosanthes kirilowii lectin alleviates diabetic nephropathy by inhibiting the LOX1/NF-κB/caspase-9 signaling pathway
title Trichosanthes kirilowii lectin alleviates diabetic nephropathy by inhibiting the LOX1/NF-κB/caspase-9 signaling pathway
title_full Trichosanthes kirilowii lectin alleviates diabetic nephropathy by inhibiting the LOX1/NF-κB/caspase-9 signaling pathway
title_fullStr Trichosanthes kirilowii lectin alleviates diabetic nephropathy by inhibiting the LOX1/NF-κB/caspase-9 signaling pathway
title_full_unstemmed Trichosanthes kirilowii lectin alleviates diabetic nephropathy by inhibiting the LOX1/NF-κB/caspase-9 signaling pathway
title_short Trichosanthes kirilowii lectin alleviates diabetic nephropathy by inhibiting the LOX1/NF-κB/caspase-9 signaling pathway
title_sort trichosanthes kirilowii lectin alleviates diabetic nephropathy by inhibiting the lox1/nf-κb/caspase-9 signaling pathway
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127671/
https://www.ncbi.nlm.nih.gov/pubmed/30038056
http://dx.doi.org/10.1042/BSR20180071
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