Endogenous Nampt upregulation is associated with diabetic nephropathy inflammatory-fibrosis through the NF-κB p65 and Sirt1 pathway; NMN alleviates diabetic nephropathy inflammatory-fibrosis by inhibiting endogenous Nampt
Nicotinamide phosphoribosyltransferase (Nampt) is a key enzyme in the nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway. Exogenous extra cellular Nampt has been reported to increase the synthesis of pro-fibrotic molecules in various types of renal cells. However, the role of endogenous N...
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| Veröffentlicht in: | Experimental and therapeutic medicine 2017-11, Vol.14 (5), p.4181-4193 |
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| creator | Chen, Ye Liang, Yuzhen Hu, Tingting Wei, Riming Cai, Congjie Wang, Ping Wang, Lingyu Qiao, Wei Feng, Leping |
| description | Nicotinamide phosphoribosyltransferase (Nampt) is a key enzyme in the nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway. Exogenous extra cellular Nampt has been reported to increase the synthesis of pro-fibrotic molecules in various types of renal cells. However, the role of endogenous Namptenzymatic activity in diabetic renal cells, particularly those associated with inflammation and fibrosis through the nuclear factor (NF)-κB p65 and sirtuin 1 (Sirt1) pathway is still unknown. In the present study, a possible mechanism by which endogenous Nampt upregulation affects the expression of pro-inflammatory and pro-fibrotic cytokines in vivo and in vitro, is reported. The present results demonstrate that the expression of vimentin and fibronectin was directly implicated in endogenous Nampt upregulation. The expression levels of Poly(ADP-ribose) polymerase-1, NF-κB p65, forkhead box protein O1 and B-cell lymphoma 2-like protein 4 were also significantly increased at 96 h compared with control group (P |
| doi_str_mv | 10.3892/etm.2017.5098 |
| format | Article |
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Exogenous extra cellular Nampt has been reported to increase the synthesis of pro-fibrotic molecules in various types of renal cells. However, the role of endogenous Namptenzymatic activity in diabetic renal cells, particularly those associated with inflammation and fibrosis through the nuclear factor (NF)-κB p65 and sirtuin 1 (Sirt1) pathway is still unknown. In the present study, a possible mechanism by which endogenous Nampt upregulation affects the expression of pro-inflammatory and pro-fibrotic cytokines in vivo and in vitro, is reported. The present results demonstrate that the expression of vimentin and fibronectin was directly implicated in endogenous Nampt upregulation. The expression levels of Poly(ADP-ribose) polymerase-1, NF-κB p65, forkhead box protein O1 and B-cell lymphoma 2-like protein 4 were also significantly increased at 96 h compared with control group (P<0.01) respectively in response to endogenous Nampt upregulation. Furthermore, the expression level of Sirt1 was significantly reduced (P<0.05), and the NAD and NADH levels, and the NAD/NADH ratio are significantly altered in STZ-induced diabetic rats (P<0.01). Treatment with FK866 and nicotinamide mononucleotide (NMN) led to downregulation of vimentin and fibronectin, respectively. These results suggest a novel role of Nampt as a pro-inflammatory cytokine of mesangial fibrotic signaling. The Nampt-NF-κB p65 and Sirt1 signaling pathway serves a pivotal role in affecting the expression of fibrosis factors in diabetic nephropathy (DN) glomerular fibrosis processing. It is also suggested that prevention of endogenous Nampt upregulation may be critical in the treatment of DN pro-inflammatory fibrosis and NMN is likely to be a potential pharmacological agent for the treatment of resistant DN nephritic fibrosis.</description><identifier>ISSN: 1792-0981</identifier><identifier>EISSN: 1792-1015</identifier><identifier>DOI: 10.3892/etm.2017.5098</identifier><identifier>PMID: 29104634</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Apoptosis ; Diabetes ; diabetic nephropathies ; Diabetic nephropathy ; Enzymes ; Experiments ; fibrosis ; Glucose ; Humidity ; Inflammation ; Insulin ; Kinases ; Medical research ; Nampt ; nuclear factor-κB p65 ; Oxidative stress ; Pathogenesis ; Proteins ; Rodents ; sirtuin 1 ; Standard deviation</subject><ispartof>Experimental and therapeutic medicine, 2017-11, Vol.14 (5), p.4181-4193</ispartof><rights>Copyright: © Chen et al.</rights><rights>Copyright Spandidos Publications UK Ltd. 2017</rights><rights>Copyright: © Chen et al. 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-fdaff9d5da9492c47f68741f953fbb55eaf7688323d36ac42c5363d231bcb2e53</citedby><cites>FETCH-LOGICAL-c445t-fdaff9d5da9492c47f68741f953fbb55eaf7688323d36ac42c5363d231bcb2e53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658765/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658765/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29104634$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Ye</creatorcontrib><creatorcontrib>Liang, Yuzhen</creatorcontrib><creatorcontrib>Hu, Tingting</creatorcontrib><creatorcontrib>Wei, Riming</creatorcontrib><creatorcontrib>Cai, Congjie</creatorcontrib><creatorcontrib>Wang, Ping</creatorcontrib><creatorcontrib>Wang, Lingyu</creatorcontrib><creatorcontrib>Qiao, Wei</creatorcontrib><creatorcontrib>Feng, Leping</creatorcontrib><title>Endogenous Nampt upregulation is associated with diabetic nephropathy inflammatory-fibrosis through the NF-κB p65 and Sirt1 pathway; NMN alleviates diabetic nephropathy inflammatory-fibrosis by inhibiting endogenous Nampt</title><title>Experimental and therapeutic medicine</title><addtitle>Exp Ther Med</addtitle><description>Nicotinamide phosphoribosyltransferase (Nampt) is a key enzyme in the nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway. Exogenous extra cellular Nampt has been reported to increase the synthesis of pro-fibrotic molecules in various types of renal cells. However, the role of endogenous Namptenzymatic activity in diabetic renal cells, particularly those associated with inflammation and fibrosis through the nuclear factor (NF)-κB p65 and sirtuin 1 (Sirt1) pathway is still unknown. In the present study, a possible mechanism by which endogenous Nampt upregulation affects the expression of pro-inflammatory and pro-fibrotic cytokines in vivo and in vitro, is reported. The present results demonstrate that the expression of vimentin and fibronectin was directly implicated in endogenous Nampt upregulation. The expression levels of Poly(ADP-ribose) polymerase-1, NF-κB p65, forkhead box protein O1 and B-cell lymphoma 2-like protein 4 were also significantly increased at 96 h compared with control group (P<0.01) respectively in response to endogenous Nampt upregulation. Furthermore, the expression level of Sirt1 was significantly reduced (P<0.05), and the NAD and NADH levels, and the NAD/NADH ratio are significantly altered in STZ-induced diabetic rats (P<0.01). Treatment with FK866 and nicotinamide mononucleotide (NMN) led to downregulation of vimentin and fibronectin, respectively. These results suggest a novel role of Nampt as a pro-inflammatory cytokine of mesangial fibrotic signaling. The Nampt-NF-κB p65 and Sirt1 signaling pathway serves a pivotal role in affecting the expression of fibrosis factors in diabetic nephropathy (DN) glomerular fibrosis processing. It is also suggested that prevention of endogenous Nampt upregulation may be critical in the treatment of DN pro-inflammatory fibrosis and NMN is likely to be a potential pharmacological agent for the treatment of resistant DN nephritic fibrosis.</description><subject>Apoptosis</subject><subject>Diabetes</subject><subject>diabetic nephropathies</subject><subject>Diabetic nephropathy</subject><subject>Enzymes</subject><subject>Experiments</subject><subject>fibrosis</subject><subject>Glucose</subject><subject>Humidity</subject><subject>Inflammation</subject><subject>Insulin</subject><subject>Kinases</subject><subject>Medical research</subject><subject>Nampt</subject><subject>nuclear factor-κB p65</subject><subject>Oxidative stress</subject><subject>Pathogenesis</subject><subject>Proteins</subject><subject>Rodents</subject><subject>sirtuin 1</subject><subject>Standard deviation</subject><issn>1792-0981</issn><issn>1792-1015</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqVklFv1SAUxxujccvco6-GxJj40muBQktMTOZypybb9cH5TGiBlqWFCnTL_Wp-CD_CPsuo93qjexMeIJzf-R8O_LPsJSxWuGbonYrjChWwWpGC1U-yY1gxlMMCkqf7fTqGR9lpCDdFGoTCuibPsyPEYFFSXB5n92srXaesmwPYiHGKYJ686uZBROMsMAGIEFxrRFQS3JnYA2lEo6JpgVVT790kYr8FxupBjKOIzm9zbRrvQkqNKT53fVoV2Fzkv35-BBMlQFgJvhkfIViS78T2PdhcbYAYBnW7FAr_U6NZAr1pTDS2A-pRNy-yZ1oMQZ3u15Ps-8X6-vxzfvn105fzs8u8LUsScy2F1kwSKVjJUFtWmtZVCTUjWDcNIUroitY1RlhiKtoStQRTLBGGTdsgRfBJ9mGnO83NqGSrbPRi4JM3o_Bb7oTh_0as6XnnbjmhpK7oIvB2L-Ddj1mFyEcTWjUMwqrUDYeMwgJjQllCXz9Cb9zsbWovUTVhJSkRTVS-o9r0TsErfbgMLPhiHp7Mwxfz8MU8iX_1dwcH-o9VEvBmB4QpfaCRLhyY9fVVXqT5W-gBMTvUdA</recordid><startdate>20171101</startdate><enddate>20171101</enddate><creator>Chen, Ye</creator><creator>Liang, Yuzhen</creator><creator>Hu, Tingting</creator><creator>Wei, Riming</creator><creator>Cai, Congjie</creator><creator>Wang, Ping</creator><creator>Wang, Lingyu</creator><creator>Qiao, Wei</creator><creator>Feng, Leping</creator><general>D.A. Spandidos</general><general>Spandidos Publications UK Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20171101</creationdate><title>Endogenous Nampt upregulation is associated with diabetic nephropathy inflammatory-fibrosis through the NF-κB p65 and Sirt1 pathway; NMN alleviates diabetic nephropathy inflammatory-fibrosis by inhibiting endogenous Nampt</title><author>Chen, Ye ; Liang, Yuzhen ; Hu, Tingting ; Wei, Riming ; Cai, Congjie ; Wang, Ping ; Wang, Lingyu ; Qiao, Wei ; Feng, Leping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-fdaff9d5da9492c47f68741f953fbb55eaf7688323d36ac42c5363d231bcb2e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Apoptosis</topic><topic>Diabetes</topic><topic>diabetic nephropathies</topic><topic>Diabetic nephropathy</topic><topic>Enzymes</topic><topic>Experiments</topic><topic>fibrosis</topic><topic>Glucose</topic><topic>Humidity</topic><topic>Inflammation</topic><topic>Insulin</topic><topic>Kinases</topic><topic>Medical research</topic><topic>Nampt</topic><topic>nuclear factor-κB p65</topic><topic>Oxidative stress</topic><topic>Pathogenesis</topic><topic>Proteins</topic><topic>Rodents</topic><topic>sirtuin 1</topic><topic>Standard deviation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Ye</creatorcontrib><creatorcontrib>Liang, Yuzhen</creatorcontrib><creatorcontrib>Hu, Tingting</creatorcontrib><creatorcontrib>Wei, Riming</creatorcontrib><creatorcontrib>Cai, Congjie</creatorcontrib><creatorcontrib>Wang, Ping</creatorcontrib><creatorcontrib>Wang, Lingyu</creatorcontrib><creatorcontrib>Qiao, Wei</creatorcontrib><creatorcontrib>Feng, Leping</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Experimental and therapeutic medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Ye</au><au>Liang, Yuzhen</au><au>Hu, Tingting</au><au>Wei, Riming</au><au>Cai, Congjie</au><au>Wang, Ping</au><au>Wang, Lingyu</au><au>Qiao, Wei</au><au>Feng, Leping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Endogenous Nampt upregulation is associated with diabetic nephropathy inflammatory-fibrosis through the NF-κB p65 and Sirt1 pathway; NMN alleviates diabetic nephropathy inflammatory-fibrosis by inhibiting endogenous Nampt</atitle><jtitle>Experimental and therapeutic medicine</jtitle><addtitle>Exp Ther Med</addtitle><date>2017-11-01</date><risdate>2017</risdate><volume>14</volume><issue>5</issue><spage>4181</spage><epage>4193</epage><pages>4181-4193</pages><issn>1792-0981</issn><eissn>1792-1015</eissn><abstract>Nicotinamide phosphoribosyltransferase (Nampt) is a key enzyme in the nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway. Exogenous extra cellular Nampt has been reported to increase the synthesis of pro-fibrotic molecules in various types of renal cells. However, the role of endogenous Namptenzymatic activity in diabetic renal cells, particularly those associated with inflammation and fibrosis through the nuclear factor (NF)-κB p65 and sirtuin 1 (Sirt1) pathway is still unknown. In the present study, a possible mechanism by which endogenous Nampt upregulation affects the expression of pro-inflammatory and pro-fibrotic cytokines in vivo and in vitro, is reported. The present results demonstrate that the expression of vimentin and fibronectin was directly implicated in endogenous Nampt upregulation. The expression levels of Poly(ADP-ribose) polymerase-1, NF-κB p65, forkhead box protein O1 and B-cell lymphoma 2-like protein 4 were also significantly increased at 96 h compared with control group (P<0.01) respectively in response to endogenous Nampt upregulation. Furthermore, the expression level of Sirt1 was significantly reduced (P<0.05), and the NAD and NADH levels, and the NAD/NADH ratio are significantly altered in STZ-induced diabetic rats (P<0.01). Treatment with FK866 and nicotinamide mononucleotide (NMN) led to downregulation of vimentin and fibronectin, respectively. These results suggest a novel role of Nampt as a pro-inflammatory cytokine of mesangial fibrotic signaling. The Nampt-NF-κB p65 and Sirt1 signaling pathway serves a pivotal role in affecting the expression of fibrosis factors in diabetic nephropathy (DN) glomerular fibrosis processing. It is also suggested that prevention of endogenous Nampt upregulation may be critical in the treatment of DN pro-inflammatory fibrosis and NMN is likely to be a potential pharmacological agent for the treatment of resistant DN nephritic fibrosis.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>29104634</pmid><doi>10.3892/etm.2017.5098</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Apoptosis Diabetes diabetic nephropathies Diabetic nephropathy Enzymes Experiments fibrosis Glucose Humidity Inflammation Insulin Kinases Medical research Nampt nuclear factor-κB p65 Oxidative stress Pathogenesis Proteins Rodents sirtuin 1 Standard deviation |
| title | Endogenous Nampt upregulation is associated with diabetic nephropathy inflammatory-fibrosis through the NF-κB p65 and Sirt1 pathway; NMN alleviates diabetic nephropathy inflammatory-fibrosis by inhibiting endogenous Nampt |
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