Sauchinone Protects Renal Mesangial Cell Dysfunction against Angiotensin II by Improving Renal Fibrosis and Inflammation
Abnormal and excessive growth of mesangial cells is important in the pathophysiologic processes of diabetes-associated interstitial fibrosis and glomerulosclerosis, leading to diabetic nephropathy, which eventually turns into end-stage renal disease. Sauchinone, a biologically-active lignan isolated...
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| description | Abnormal and excessive growth of mesangial cells is important in the pathophysiologic processes of diabetes-associated interstitial fibrosis and glomerulosclerosis, leading to diabetic nephropathy, which eventually turns into end-stage renal disease. Sauchinone, a biologically-active lignan isolated from aerial parts of
, has anti-inflammatory and anti-viral activities effects on various cell types. However, there are no studies reporting the effects of sauchinone on diabetic nephropathy. The present study aims to investigate the role of sauchinone in mesangial cell proliferation and fibrosis induced by angiotensin II, as well as the underlying mechanisms of these processes. Human renal mesangial cells were induced by angiotensin II (AngII, 10 μM) in the presence or absence of sauchinone (0.1-1 μM) and incubated for 48 h. In this study, we found that AngII induced mesangial cell proliferation, while treatment with sauchinone inhibited the cell proliferation in a dose-dependent manner. Pre-treatment with sauchinone induced down-regulation of cyclins/CDKs and up-regulation of CDK inhibitor, p21, and p27
expression. In addition, AngII-enhanced expression of fibrosis biomarkers such as fibronectin, collagen IV, and connective tissue growth factor (CTGF), which was markedly attenuated by sauchinone. Sauchinone also decreased AngII-induced TGF-β1 and Smad-2, Smad-3, and Smad-4 expression. This study further revealed that sauchinone ameliorated AngII-induced mesangial inflammation through disturbing activation of inflammatory factors, and NLRP3 inflammasome, which is composed of the NLRP3 protein, procaspase-1, and apoptosis-associated speck-like protein containing a CARD (ASC). Moreover, pretreatment of sauchinone inhibited NF-κB translocation and ROS production in AngII-exposed mesangial cells. These data suggest that sauchinone has a protective effect on renal proliferation, fibrosis and inflammation. Therefore, sauchinone might be a potential pharmacological agent in prevention of AngII-induced renal damage leading to diabetic nephropathy. |
| doi_str_mv | 10.3390/ijms21197003 |
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, has anti-inflammatory and anti-viral activities effects on various cell types. However, there are no studies reporting the effects of sauchinone on diabetic nephropathy. The present study aims to investigate the role of sauchinone in mesangial cell proliferation and fibrosis induced by angiotensin II, as well as the underlying mechanisms of these processes. Human renal mesangial cells were induced by angiotensin II (AngII, 10 μM) in the presence or absence of sauchinone (0.1-1 μM) and incubated for 48 h. In this study, we found that AngII induced mesangial cell proliferation, while treatment with sauchinone inhibited the cell proliferation in a dose-dependent manner. Pre-treatment with sauchinone induced down-regulation of cyclins/CDKs and up-regulation of CDK inhibitor, p21, and p27
expression. In addition, AngII-enhanced expression of fibrosis biomarkers such as fibronectin, collagen IV, and connective tissue growth factor (CTGF), which was markedly attenuated by sauchinone. Sauchinone also decreased AngII-induced TGF-β1 and Smad-2, Smad-3, and Smad-4 expression. This study further revealed that sauchinone ameliorated AngII-induced mesangial inflammation through disturbing activation of inflammatory factors, and NLRP3 inflammasome, which is composed of the NLRP3 protein, procaspase-1, and apoptosis-associated speck-like protein containing a CARD (ASC). Moreover, pretreatment of sauchinone inhibited NF-κB translocation and ROS production in AngII-exposed mesangial cells. These data suggest that sauchinone has a protective effect on renal proliferation, fibrosis and inflammation. Therefore, sauchinone might be a potential pharmacological agent in prevention of AngII-induced renal damage leading to diabetic nephropathy.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms21197003</identifier><identifier>PMID: 32977573</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Angiotensin ; Angiotensin II ; Angiotensin II - adverse effects ; Angiotensin II - pharmacology ; Antiviral agents ; Apoptosis ; Benzopyrans - pharmacology ; Caspase-1 ; Cell cycle ; Cell growth ; Cell Line ; Cell proliferation ; Collagen (type IV) ; Connective tissue growth factor ; Cyclin-dependent kinase inhibitor p27 ; Cyclins ; Diabetes ; Diabetes mellitus ; Diabetic Nephropathies - drug therapy ; Diabetic Nephropathies - metabolism ; Diabetic Nephropathies - pathology ; Diabetic nephropathy ; Dioxoles - pharmacology ; End-stage renal disease ; Fibronectin ; Fibrosis ; Gene Expression Regulation - drug effects ; Growth factors ; Health aspects ; Humans ; Inflammasomes ; Inflammation ; Inflammation - chemically induced ; Inflammation - drug therapy ; Inflammation - metabolism ; Inflammation - pathology ; Kidney diseases ; Lignans ; Lignin ; Mesangial cells ; Mesangial Cells - metabolism ; Mesangial Cells - pathology ; Nephropathy ; NF-κB protein ; Pathogenesis ; Phase transitions ; Physiological aspects ; Protein expression ; Proteins ; Renal function ; Smad protein ; Transforming growth factor-b1 ; Wound healing</subject><ispartof>International journal of molecular sciences, 2020-10, Vol.21 (19), p.7003</ispartof><rights>COPYRIGHT 2020 MDPI AG</rights><rights>2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-ceb7731d64e70432f5417593558f34c9805c1ba139b695440a4e99b67887291b3</citedby><cites>FETCH-LOGICAL-c479t-ceb7731d64e70432f5417593558f34c9805c1ba139b695440a4e99b67887291b3</cites><orcidid>0000-0002-9347-8606</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583825/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583825/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32977573$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yoon, Jung Joo</creatorcontrib><creatorcontrib>Lee, Hyeon Kyoung</creatorcontrib><creatorcontrib>Kim, Hye Yoom</creatorcontrib><creatorcontrib>Han, Byung Hyuk</creatorcontrib><creatorcontrib>Lee, Ho Sub</creatorcontrib><creatorcontrib>Lee, Yun Jung</creatorcontrib><creatorcontrib>Kang, Dae Gill</creatorcontrib><title>Sauchinone Protects Renal Mesangial Cell Dysfunction against Angiotensin II by Improving Renal Fibrosis and Inflammation</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Abnormal and excessive growth of mesangial cells is important in the pathophysiologic processes of diabetes-associated interstitial fibrosis and glomerulosclerosis, leading to diabetic nephropathy, which eventually turns into end-stage renal disease. Sauchinone, a biologically-active lignan isolated from aerial parts of
, has anti-inflammatory and anti-viral activities effects on various cell types. However, there are no studies reporting the effects of sauchinone on diabetic nephropathy. The present study aims to investigate the role of sauchinone in mesangial cell proliferation and fibrosis induced by angiotensin II, as well as the underlying mechanisms of these processes. Human renal mesangial cells were induced by angiotensin II (AngII, 10 μM) in the presence or absence of sauchinone (0.1-1 μM) and incubated for 48 h. In this study, we found that AngII induced mesangial cell proliferation, while treatment with sauchinone inhibited the cell proliferation in a dose-dependent manner. Pre-treatment with sauchinone induced down-regulation of cyclins/CDKs and up-regulation of CDK inhibitor, p21, and p27
expression. In addition, AngII-enhanced expression of fibrosis biomarkers such as fibronectin, collagen IV, and connective tissue growth factor (CTGF), which was markedly attenuated by sauchinone. Sauchinone also decreased AngII-induced TGF-β1 and Smad-2, Smad-3, and Smad-4 expression. This study further revealed that sauchinone ameliorated AngII-induced mesangial inflammation through disturbing activation of inflammatory factors, and NLRP3 inflammasome, which is composed of the NLRP3 protein, procaspase-1, and apoptosis-associated speck-like protein containing a CARD (ASC). Moreover, pretreatment of sauchinone inhibited NF-κB translocation and ROS production in AngII-exposed mesangial cells. These data suggest that sauchinone has a protective effect on renal proliferation, fibrosis and inflammation. Therefore, sauchinone might be a potential pharmacological agent in prevention of AngII-induced renal damage leading to diabetic nephropathy.</description><subject>Angiotensin</subject><subject>Angiotensin II</subject><subject>Angiotensin II - adverse effects</subject><subject>Angiotensin II - pharmacology</subject><subject>Antiviral agents</subject><subject>Apoptosis</subject><subject>Benzopyrans - pharmacology</subject><subject>Caspase-1</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cell Line</subject><subject>Cell proliferation</subject><subject>Collagen (type IV)</subject><subject>Connective tissue growth factor</subject><subject>Cyclin-dependent kinase inhibitor p27</subject><subject>Cyclins</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetic Nephropathies - drug therapy</subject><subject>Diabetic Nephropathies - metabolism</subject><subject>Diabetic Nephropathies - pathology</subject><subject>Diabetic nephropathy</subject><subject>Dioxoles - pharmacology</subject><subject>End-stage renal disease</subject><subject>Fibronectin</subject><subject>Fibrosis</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Growth factors</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Inflammasomes</subject><subject>Inflammation</subject><subject>Inflammation - chemically induced</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - metabolism</subject><subject>Inflammation - pathology</subject><subject>Kidney diseases</subject><subject>Lignans</subject><subject>Lignin</subject><subject>Mesangial cells</subject><subject>Mesangial Cells - metabolism</subject><subject>Mesangial Cells - pathology</subject><subject>Nephropathy</subject><subject>NF-κB protein</subject><subject>Pathogenesis</subject><subject>Phase transitions</subject><subject>Physiological aspects</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Renal function</subject><subject>Smad protein</subject><subject>Transforming growth factor-b1</subject><subject>Wound healing</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptkUtLJDEUhYOMqKPuXA8Bt9OaZ6WyGWh6fBQoio91SKVTZZqqpE2qxP73k8Yep4Uhi1xyz_m4NweAE4zOKJXo3C36RDCWAiG6Aw4wI2SCUCG-bdX74HtKC4QIJVzugX1KpBBc0APw_qhH8-J88BbexzBYMyT4YL3u4K1N2rcuVzPbdfD3KjWjN4MLHupWO58GOM397PHJeVhVsF7Bql_G8OZ8u4FcujqG5BLUfg4r33S67_WacQR2G90le7y5D8Hz5cXT7Hpyc3dVzaY3E8OEHCbG1kJQPC-YFYhR0nCGBZeU87KhzMgScYNrjamsC8kZQ5pZmWtRloJIXNND8OuDuxzr3s6N9UPUnVpG1-u4UkE79bXj3Ytqw5sSvKQl4RlwugHE8DraNKhFGGPeLSnCWVkUEjH0T9Xqzirnm5BhpnfJqGnBiKSYszXr7D-qfOa2dyZn0Lj8_sXw88Ng8i-maJvPwTFS6_jVdvxZ_mN72U_x37zpHzVZqvA</recordid><startdate>20201001</startdate><enddate>20201001</enddate><creator>Yoon, Jung Joo</creator><creator>Lee, Hyeon Kyoung</creator><creator>Kim, Hye Yoom</creator><creator>Han, Byung Hyuk</creator><creator>Lee, Ho Sub</creator><creator>Lee, Yun Jung</creator><creator>Kang, Dae Gill</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9347-8606</orcidid></search><sort><creationdate>20201001</creationdate><title>Sauchinone Protects Renal Mesangial Cell Dysfunction against Angiotensin II by Improving Renal Fibrosis and Inflammation</title><author>Yoon, Jung Joo ; Lee, Hyeon Kyoung ; Kim, Hye Yoom ; Han, Byung Hyuk ; Lee, Ho Sub ; Lee, Yun Jung ; Kang, Dae Gill</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-ceb7731d64e70432f5417593558f34c9805c1ba139b695440a4e99b67887291b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Angiotensin</topic><topic>Angiotensin II</topic><topic>Angiotensin II - adverse effects</topic><topic>Angiotensin II - pharmacology</topic><topic>Antiviral agents</topic><topic>Apoptosis</topic><topic>Benzopyrans - pharmacology</topic><topic>Caspase-1</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Cell Line</topic><topic>Cell proliferation</topic><topic>Collagen (type IV)</topic><topic>Connective tissue growth factor</topic><topic>Cyclin-dependent kinase inhibitor p27</topic><topic>Cyclins</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetic Nephropathies - drug therapy</topic><topic>Diabetic Nephropathies - metabolism</topic><topic>Diabetic Nephropathies - pathology</topic><topic>Diabetic nephropathy</topic><topic>Dioxoles - pharmacology</topic><topic>End-stage renal disease</topic><topic>Fibronectin</topic><topic>Fibrosis</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Growth factors</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Inflammasomes</topic><topic>Inflammation</topic><topic>Inflammation - chemically induced</topic><topic>Inflammation - drug therapy</topic><topic>Inflammation - metabolism</topic><topic>Inflammation - pathology</topic><topic>Kidney diseases</topic><topic>Lignans</topic><topic>Lignin</topic><topic>Mesangial cells</topic><topic>Mesangial Cells - metabolism</topic><topic>Mesangial Cells - pathology</topic><topic>Nephropathy</topic><topic>NF-κB protein</topic><topic>Pathogenesis</topic><topic>Phase transitions</topic><topic>Physiological aspects</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>Renal function</topic><topic>Smad protein</topic><topic>Transforming growth factor-b1</topic><topic>Wound healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yoon, Jung Joo</creatorcontrib><creatorcontrib>Lee, Hyeon Kyoung</creatorcontrib><creatorcontrib>Kim, Hye Yoom</creatorcontrib><creatorcontrib>Han, Byung Hyuk</creatorcontrib><creatorcontrib>Lee, Ho Sub</creatorcontrib><creatorcontrib>Lee, Yun Jung</creatorcontrib><creatorcontrib>Kang, Dae Gill</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</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>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yoon, Jung Joo</au><au>Lee, Hyeon Kyoung</au><au>Kim, Hye Yoom</au><au>Han, Byung Hyuk</au><au>Lee, Ho Sub</au><au>Lee, Yun Jung</au><au>Kang, Dae Gill</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sauchinone Protects Renal Mesangial Cell Dysfunction against Angiotensin II by Improving Renal Fibrosis and Inflammation</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2020-10-01</date><risdate>2020</risdate><volume>21</volume><issue>19</issue><spage>7003</spage><pages>7003-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Abnormal and excessive growth of mesangial cells is important in the pathophysiologic processes of diabetes-associated interstitial fibrosis and glomerulosclerosis, leading to diabetic nephropathy, which eventually turns into end-stage renal disease. Sauchinone, a biologically-active lignan isolated from aerial parts of
, has anti-inflammatory and anti-viral activities effects on various cell types. However, there are no studies reporting the effects of sauchinone on diabetic nephropathy. The present study aims to investigate the role of sauchinone in mesangial cell proliferation and fibrosis induced by angiotensin II, as well as the underlying mechanisms of these processes. Human renal mesangial cells were induced by angiotensin II (AngII, 10 μM) in the presence or absence of sauchinone (0.1-1 μM) and incubated for 48 h. In this study, we found that AngII induced mesangial cell proliferation, while treatment with sauchinone inhibited the cell proliferation in a dose-dependent manner. Pre-treatment with sauchinone induced down-regulation of cyclins/CDKs and up-regulation of CDK inhibitor, p21, and p27
expression. In addition, AngII-enhanced expression of fibrosis biomarkers such as fibronectin, collagen IV, and connective tissue growth factor (CTGF), which was markedly attenuated by sauchinone. Sauchinone also decreased AngII-induced TGF-β1 and Smad-2, Smad-3, and Smad-4 expression. This study further revealed that sauchinone ameliorated AngII-induced mesangial inflammation through disturbing activation of inflammatory factors, and NLRP3 inflammasome, which is composed of the NLRP3 protein, procaspase-1, and apoptosis-associated speck-like protein containing a CARD (ASC). Moreover, pretreatment of sauchinone inhibited NF-κB translocation and ROS production in AngII-exposed mesangial cells. These data suggest that sauchinone has a protective effect on renal proliferation, fibrosis and inflammation. Therefore, sauchinone might be a potential pharmacological agent in prevention of AngII-induced renal damage leading to diabetic nephropathy.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>32977573</pmid><doi>10.3390/ijms21197003</doi><orcidid>https://orcid.org/0000-0002-9347-8606</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Angiotensin Angiotensin II Angiotensin II - adverse effects Angiotensin II - pharmacology Antiviral agents Apoptosis Benzopyrans - pharmacology Caspase-1 Cell cycle Cell growth Cell Line Cell proliferation Collagen (type IV) Connective tissue growth factor Cyclin-dependent kinase inhibitor p27 Cyclins Diabetes Diabetes mellitus Diabetic Nephropathies - drug therapy Diabetic Nephropathies - metabolism Diabetic Nephropathies - pathology Diabetic nephropathy Dioxoles - pharmacology End-stage renal disease Fibronectin Fibrosis Gene Expression Regulation - drug effects Growth factors Health aspects Humans Inflammasomes Inflammation Inflammation - chemically induced Inflammation - drug therapy Inflammation - metabolism Inflammation - pathology Kidney diseases Lignans Lignin Mesangial cells Mesangial Cells - metabolism Mesangial Cells - pathology Nephropathy NF-κB protein Pathogenesis Phase transitions Physiological aspects Protein expression Proteins Renal function Smad protein Transforming growth factor-b1 Wound healing |
| title | Sauchinone Protects Renal Mesangial Cell Dysfunction against Angiotensin II by Improving Renal Fibrosis and Inflammation |
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