Xiao-Shen-Formula, a Traditional Chinese Medicine, Improves Glomerular Hyper-Filtration in Diabetic Nephropathy via Inhibiting Arginase Activation and Heparanase Expression
Hyperglycemia induces glomerular hyper-filtration, which contributes to the development of diabetic nephropathy (DN), a condition that remains a challenge for treatment. The present study investigated the effect of Xiao-Shen-Formula (XSF) used for treatment of renal injury in type 1 DN mice model in...
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Frontiers Media S.A.
2018-09-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2018.01195/full |
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| author | Xiaofei An Xiaofei An Maoxiang Zhang Maoxiang Zhang Sisi Zhou Tian Lu Yongjun Chen Yongjun Chen Lin Yao Lin Yao |
| author_facet | Xiaofei An Xiaofei An Maoxiang Zhang Maoxiang Zhang Sisi Zhou Tian Lu Yongjun Chen Yongjun Chen Lin Yao Lin Yao |
| author_sort | Xiaofei An |
| collection | DOAJ |
| description | Hyperglycemia induces glomerular hyper-filtration, which contributes to the development of diabetic nephropathy (DN), a condition that remains a challenge for treatment. The present study investigated the effect of Xiao-Shen-Formula (XSF) used for treatment of renal injury in type 1 DN mice model induced by streptozotocin (STZ) and its underlying mechanism in cultured human glomerular endothelial cell (hGECs). Studies were performed using control, diabetic DN, DN treated with XSF groups (1 g/kg/d, LXSF or 3 g/kg/d, HXSF) for 6 weeks and hGECs were post-treated with mice serum containing HXSF (MS-HXSF) and arginase inhibitor (ABH, 100 μM) in high glucose medium. HXSF treatment restored STZ-induced renal hyper-filtration, glomerulosclerosis, renal microvascular remodeling and the increased levels of systemic reactive oxidative species and inflammatory cytokines, accompanied by preventing the decreased expression of glomerular heparin sulfate and the increased levels of cortical heparanase and argianse2 protein and arginase activity. In hGECs study, MS-HXSF ameliorated the enhancement in arginase activity, the protein/mRNA expression of heparanase, mRNA levels of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, monocyte chemoattractant protein-1 and permeability of hGECs monolayers as well as the depression of nitric oxide production. Besides all these protective effects, XSF blunted the mRNA expression of TNF-α in vivo and vitro studies as well, which was not changed by the post-treatment of ABH or HXSF plus ABH. This study demonstrated that the protective effect of XSF might be related with vascular prevention, anti-inflammation and anti-oxidation through intervening multi-targets including glomerular endothelial arginase-heparanase signaling pathway in DN model. |
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| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-12T11:58:43Z |
| publishDate | 2018-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Physiology |
| spelling | doaj.art-07e9dfef694e4e43a6d80b0999b418742022-12-22T03:33:56ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-09-01910.3389/fphys.2018.01195347896Xiao-Shen-Formula, a Traditional Chinese Medicine, Improves Glomerular Hyper-Filtration in Diabetic Nephropathy via Inhibiting Arginase Activation and Heparanase ExpressionXiaofei An0Xiaofei An1Maoxiang Zhang2Maoxiang Zhang3Sisi Zhou4Tian Lu5Yongjun Chen6Yongjun Chen7Lin Yao8Lin Yao9School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaSouth China Research Center for Acupuncture and Moxibustion, Guangzhou University of Chinese Medicine, Guangzhou, ChinaMedical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaSouth China Research Center for Acupuncture and Moxibustion, Guangzhou University of Chinese Medicine, Guangzhou, ChinaMedical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaSouth China Research Center for Acupuncture and Moxibustion, Guangzhou University of Chinese Medicine, Guangzhou, ChinaHyperglycemia induces glomerular hyper-filtration, which contributes to the development of diabetic nephropathy (DN), a condition that remains a challenge for treatment. The present study investigated the effect of Xiao-Shen-Formula (XSF) used for treatment of renal injury in type 1 DN mice model induced by streptozotocin (STZ) and its underlying mechanism in cultured human glomerular endothelial cell (hGECs). Studies were performed using control, diabetic DN, DN treated with XSF groups (1 g/kg/d, LXSF or 3 g/kg/d, HXSF) for 6 weeks and hGECs were post-treated with mice serum containing HXSF (MS-HXSF) and arginase inhibitor (ABH, 100 μM) in high glucose medium. HXSF treatment restored STZ-induced renal hyper-filtration, glomerulosclerosis, renal microvascular remodeling and the increased levels of systemic reactive oxidative species and inflammatory cytokines, accompanied by preventing the decreased expression of glomerular heparin sulfate and the increased levels of cortical heparanase and argianse2 protein and arginase activity. In hGECs study, MS-HXSF ameliorated the enhancement in arginase activity, the protein/mRNA expression of heparanase, mRNA levels of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, monocyte chemoattractant protein-1 and permeability of hGECs monolayers as well as the depression of nitric oxide production. Besides all these protective effects, XSF blunted the mRNA expression of TNF-α in vivo and vitro studies as well, which was not changed by the post-treatment of ABH or HXSF plus ABH. This study demonstrated that the protective effect of XSF might be related with vascular prevention, anti-inflammation and anti-oxidation through intervening multi-targets including glomerular endothelial arginase-heparanase signaling pathway in DN model.https://www.frontiersin.org/article/10.3389/fphys.2018.01195/fulldiabetic nephropathyglomerular hyper-filtrationXiao-Shen-Formulaarginasenitric oxideheparanase |
| spellingShingle | Xiaofei An Xiaofei An Maoxiang Zhang Maoxiang Zhang Sisi Zhou Tian Lu Yongjun Chen Yongjun Chen Lin Yao Lin Yao Xiao-Shen-Formula, a Traditional Chinese Medicine, Improves Glomerular Hyper-Filtration in Diabetic Nephropathy via Inhibiting Arginase Activation and Heparanase Expression Frontiers in Physiology diabetic nephropathy glomerular hyper-filtration Xiao-Shen-Formula arginase nitric oxide heparanase |
| title | Xiao-Shen-Formula, a Traditional Chinese Medicine, Improves Glomerular Hyper-Filtration in Diabetic Nephropathy via Inhibiting Arginase Activation and Heparanase Expression |
| title_full | Xiao-Shen-Formula, a Traditional Chinese Medicine, Improves Glomerular Hyper-Filtration in Diabetic Nephropathy via Inhibiting Arginase Activation and Heparanase Expression |
| title_fullStr | Xiao-Shen-Formula, a Traditional Chinese Medicine, Improves Glomerular Hyper-Filtration in Diabetic Nephropathy via Inhibiting Arginase Activation and Heparanase Expression |
| title_full_unstemmed | Xiao-Shen-Formula, a Traditional Chinese Medicine, Improves Glomerular Hyper-Filtration in Diabetic Nephropathy via Inhibiting Arginase Activation and Heparanase Expression |
| title_short | Xiao-Shen-Formula, a Traditional Chinese Medicine, Improves Glomerular Hyper-Filtration in Diabetic Nephropathy via Inhibiting Arginase Activation and Heparanase Expression |
| title_sort | xiao shen formula a traditional chinese medicine improves glomerular hyper filtration in diabetic nephropathy via inhibiting arginase activation and heparanase expression |
| topic | diabetic nephropathy glomerular hyper-filtration Xiao-Shen-Formula arginase nitric oxide heparanase |
| url | https://www.frontiersin.org/article/10.3389/fphys.2018.01195/full |
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