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FcgRIII Deficiency and FcgRIIb Defeciency Promote Renal Injury in Diabetic Mice

The immune system is involved in the development of diabetes complications and IgG Fc gamma receptors (FcgRs) are key immune receptors responsible for the effective control of both humoral and innate immunity. We investigated the effects of members of the FcgR superfamily into both the streptozotoci...

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Autores principales: Zhang, Rui, Wang, Tingli, Yin, Qinhua, Zhang, Junlin, Li, Li, Guo, Ruikun, Han, Qianqian, Li, Hanyu, Wang, Yiting, Wang, Jiali, Gurung, Pramesh, Lu, Yanrong, Cheng, Jingqiu, Bai, Lin, Zhang, Jie, Liu, Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724446/
https://www.ncbi.nlm.nih.gov/pubmed/31534958
http://dx.doi.org/10.1155/2019/3514574
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author Zhang, Rui
Wang, Tingli
Yin, Qinhua
Zhang, Junlin
Li, Li
Guo, Ruikun
Han, Qianqian
Li, Hanyu
Wang, Yiting
Wang, Jiali
Gurung, Pramesh
Lu, Yanrong
Cheng, Jingqiu
Bai, Lin
Zhang, Jie
Liu, Fang
author_facet Zhang, Rui
Wang, Tingli
Yin, Qinhua
Zhang, Junlin
Li, Li
Guo, Ruikun
Han, Qianqian
Li, Hanyu
Wang, Yiting
Wang, Jiali
Gurung, Pramesh
Lu, Yanrong
Cheng, Jingqiu
Bai, Lin
Zhang, Jie
Liu, Fang
author_sort Zhang, Rui
collection PubMed
description The immune system is involved in the development of diabetes complications and IgG Fc gamma receptors (FcgRs) are key immune receptors responsible for the effective control of both humoral and innate immunity. We investigated the effects of members of the FcgR superfamily into both the streptozotocin plus high fat-induced type 2 diabetes and high fat diet (HFD) models. FcgRIII(−/−) diabetic mice and FcgRIIb(−/−) diabetic mice had elevated levels of serum creatinine compared with wildtype (WT) diabetic mice. Renal histology of diabetic FcgRIII knockout and FcgRIIb knockout mice showed mesangial expansion and GBM thickening; the mechanistic study indicated a higher expression of TGF-β1, TNF-α, and p-NFκB-p65 compared with wild type mouse. The HFD mouse with FcgRIII knockout or FcgRIIb knockout had increased biochemical and renal injury factors, but oxLDL deposition was higher than in FcgRIII(−/−) diabetic mice and FcgRIIb(−/−) diabetic mice. In vitro we further examined the mechanism by which the Fc gamma receptor promoted renal injury and transfected glomerular mesangial cells (GMCs) with FcgRI siRNA attenuated the level of TGF-β1, TNF-α expression. In summary, FcgRI knockdown downregulated kidney inflammation and fibrosis and FcgRIIb knockout accelerated inflammation, fibrosis, and the anomalous deposition of oxLDL whereas FcgRIII deficiency failed to protect kidney from diabetic renal injury. These observations suggested that FcgRs might represent a novel target for the therapeutic intervention of diabetic nephropathy.
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spelling pubmed-67244462019-09-18 FcgRIII Deficiency and FcgRIIb Defeciency Promote Renal Injury in Diabetic Mice Zhang, Rui Wang, Tingli Yin, Qinhua Zhang, Junlin Li, Li Guo, Ruikun Han, Qianqian Li, Hanyu Wang, Yiting Wang, Jiali Gurung, Pramesh Lu, Yanrong Cheng, Jingqiu Bai, Lin Zhang, Jie Liu, Fang Biomed Res Int Research Article The immune system is involved in the development of diabetes complications and IgG Fc gamma receptors (FcgRs) are key immune receptors responsible for the effective control of both humoral and innate immunity. We investigated the effects of members of the FcgR superfamily into both the streptozotocin plus high fat-induced type 2 diabetes and high fat diet (HFD) models. FcgRIII(−/−) diabetic mice and FcgRIIb(−/−) diabetic mice had elevated levels of serum creatinine compared with wildtype (WT) diabetic mice. Renal histology of diabetic FcgRIII knockout and FcgRIIb knockout mice showed mesangial expansion and GBM thickening; the mechanistic study indicated a higher expression of TGF-β1, TNF-α, and p-NFκB-p65 compared with wild type mouse. The HFD mouse with FcgRIII knockout or FcgRIIb knockout had increased biochemical and renal injury factors, but oxLDL deposition was higher than in FcgRIII(−/−) diabetic mice and FcgRIIb(−/−) diabetic mice. In vitro we further examined the mechanism by which the Fc gamma receptor promoted renal injury and transfected glomerular mesangial cells (GMCs) with FcgRI siRNA attenuated the level of TGF-β1, TNF-α expression. In summary, FcgRI knockdown downregulated kidney inflammation and fibrosis and FcgRIIb knockout accelerated inflammation, fibrosis, and the anomalous deposition of oxLDL whereas FcgRIII deficiency failed to protect kidney from diabetic renal injury. These observations suggested that FcgRs might represent a novel target for the therapeutic intervention of diabetic nephropathy. Hindawi 2019-08-22 /pmc/articles/PMC6724446/ /pubmed/31534958 http://dx.doi.org/10.1155/2019/3514574 Text en Copyright © 2019 Rui Zhang et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhang, Rui
Wang, Tingli
Yin, Qinhua
Zhang, Junlin
Li, Li
Guo, Ruikun
Han, Qianqian
Li, Hanyu
Wang, Yiting
Wang, Jiali
Gurung, Pramesh
Lu, Yanrong
Cheng, Jingqiu
Bai, Lin
Zhang, Jie
Liu, Fang
FcgRIII Deficiency and FcgRIIb Defeciency Promote Renal Injury in Diabetic Mice
title FcgRIII Deficiency and FcgRIIb Defeciency Promote Renal Injury in Diabetic Mice
title_full FcgRIII Deficiency and FcgRIIb Defeciency Promote Renal Injury in Diabetic Mice
title_fullStr FcgRIII Deficiency and FcgRIIb Defeciency Promote Renal Injury in Diabetic Mice
title_full_unstemmed FcgRIII Deficiency and FcgRIIb Defeciency Promote Renal Injury in Diabetic Mice
title_short FcgRIII Deficiency and FcgRIIb Defeciency Promote Renal Injury in Diabetic Mice
title_sort fcgriii deficiency and fcgriib defeciency promote renal injury in diabetic mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724446/
https://www.ncbi.nlm.nih.gov/pubmed/31534958
http://dx.doi.org/10.1155/2019/3514574
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