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TLR4/NF-κB Signaling Induces GSDMD-Related Pyroptosis in Tubular Cells in Diabetic Kidney Disease
Gasdermin D (GSDMD) has been proven to be a key protein in the activation of pyroptosis. Pyroptosis of renal tubular epithelial cells contributes to the progression of tubular injury in kidney diseases. However, it remains elusive whether and how GSDMD is involved in the regulation of diabetic kidne...
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Published in: | Frontiers in endocrinology (Lausanne) 2019-09, Vol.10, p.603-603 |
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description | Gasdermin D (GSDMD) has been proven to be a key protein in the activation of pyroptosis. Pyroptosis of renal tubular epithelial cells contributes to the progression of tubular injury in kidney diseases. However, it remains elusive whether and how GSDMD is involved in the regulation of diabetic kidney disease (DKD). In this study, we found that tubular injury is accompanied by the up-regulation of Toll-like receptor 4 (TLR4) and GSDMD in patients with diabetic kidney disease. In addition, we discovered that the expressions of cleaved Caspase-1, active N-terminal fragments of GSDMD (GSDMD-NT), IL-18, and the secretion of IL-1β also increased in the kidneys of db/db mice. These changes were partially ameliorated following intraperitoneal injection of TAK-242, an inhibitor of TLR4. Similar results were observed in human tubular cells (HK-2) subjected to high-glucose (HG) conditions and treated with TAK-242 or parthenolide (inhibitor of NF-κB) by Western blot, Enzyme-linked immunosorbent assay (ELISA), and flow cytometry. These results indicated that TLR4/NF-κB signaling could induce GSDMD-mediated pyroptosis in tubular cells in DKD. |
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Pyroptosis of renal tubular epithelial cells contributes to the progression of tubular injury in kidney diseases. However, it remains elusive whether and how GSDMD is involved in the regulation of diabetic kidney disease (DKD). In this study, we found that tubular injury is accompanied by the up-regulation of Toll-like receptor 4 (TLR4) and GSDMD in patients with diabetic kidney disease. In addition, we discovered that the expressions of cleaved Caspase-1, active N-terminal fragments of GSDMD (GSDMD-NT), IL-18, and the secretion of IL-1β also increased in the kidneys of db/db mice. These changes were partially ameliorated following intraperitoneal injection of TAK-242, an inhibitor of TLR4. Similar results were observed in human tubular cells (HK-2) subjected to high-glucose (HG) conditions and treated with TAK-242 or parthenolide (inhibitor of NF-κB) by Western blot, Enzyme-linked immunosorbent assay (ELISA), and flow cytometry. These results indicated that TLR4/NF-κB signaling could induce GSDMD-mediated pyroptosis in tubular cells in DKD.</description><identifier>ISSN: 1664-2392</identifier><identifier>EISSN: 1664-2392</identifier><identifier>DOI: 10.3389/fendo.2019.00603</identifier><identifier>PMID: 31608008</identifier><language>eng</language><publisher>Frontiers Media S.A</publisher><subject>diabetic kidney disease ; Endocrinology ; gasdermin-D ; pyroptosis ; Toll-like receptor-4 ; tubular injury</subject><ispartof>Frontiers in endocrinology (Lausanne), 2019-09, Vol.10, p.603-603</ispartof><rights>Copyright © 2019 Wang, Zhu, Yuan, Wen, Liu, Wang, Qu, Li, Liu, Sun and Liu. 2019 Wang, Zhu, Yuan, Wen, Liu, Wang, Qu, Li, Liu, Sun and Liu</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-284d00f1fce2692275b5deb5a743b28038d376ba13462f2f493433bc507f6f033</citedby><cites>FETCH-LOGICAL-c439t-284d00f1fce2692275b5deb5a743b28038d376ba13462f2f493433bc507f6f033</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/PMC6761221/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761221/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids></links><search><creatorcontrib>Wang, Youliang</creatorcontrib><creatorcontrib>Zhu, Xuejing</creatorcontrib><creatorcontrib>Yuan, Shuguang</creatorcontrib><creatorcontrib>Wen, Si</creatorcontrib><creatorcontrib>Liu, Xuemei</creatorcontrib><creatorcontrib>Wang, Chang</creatorcontrib><creatorcontrib>Qu, Zhong</creatorcontrib><creatorcontrib>Li, Jun</creatorcontrib><creatorcontrib>Liu, Hong</creatorcontrib><creatorcontrib>Sun, Lin</creatorcontrib><creatorcontrib>Liu, Fuyou</creatorcontrib><title>TLR4/NF-κB Signaling Induces GSDMD-Related Pyroptosis in Tubular Cells in Diabetic Kidney Disease</title><title>Frontiers in endocrinology (Lausanne)</title><description>Gasdermin D (GSDMD) has been proven to be a key protein in the activation of pyroptosis. Pyroptosis of renal tubular epithelial cells contributes to the progression of tubular injury in kidney diseases. However, it remains elusive whether and how GSDMD is involved in the regulation of diabetic kidney disease (DKD). In this study, we found that tubular injury is accompanied by the up-regulation of Toll-like receptor 4 (TLR4) and GSDMD in patients with diabetic kidney disease. In addition, we discovered that the expressions of cleaved Caspase-1, active N-terminal fragments of GSDMD (GSDMD-NT), IL-18, and the secretion of IL-1β also increased in the kidneys of db/db mice. These changes were partially ameliorated following intraperitoneal injection of TAK-242, an inhibitor of TLR4. Similar results were observed in human tubular cells (HK-2) subjected to high-glucose (HG) conditions and treated with TAK-242 or parthenolide (inhibitor of NF-κB) by Western blot, Enzyme-linked immunosorbent assay (ELISA), and flow cytometry. These results indicated that TLR4/NF-κB signaling could induce GSDMD-mediated pyroptosis in tubular cells in DKD.</description><subject>diabetic kidney disease</subject><subject>Endocrinology</subject><subject>gasdermin-D</subject><subject>pyroptosis</subject><subject>Toll-like receptor-4</subject><subject>tubular injury</subject><issn>1664-2392</issn><issn>1664-2392</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNpVkc1uGyEUhVHVqonS7LucZTfjAJdhZjaVWrtJrLo_Stw1guHiEo0HF2Yq-dX6EH2mYDuqGjZcDkcf93IIecvoDKBprxwONsw4Ze2MUknhBTlnUoqSQ8tf_lefkcuUHmheInvb5jU5AyZpQ2lzTsx6dSeuvl6Xf_98LO79ZtC9HzbFcrBTh6m4uV98WZR32OsRbfF9H8NuDMmnwg_FejJTr2Mxx74_CguvDY6-Kz57O-A-nxPqhG_IK6f7hJdP-wX5cf1pPb8tV99ulvMPq7IT0I4lb4Sl1DHXIZct53VlKoum0rUAwxsKjYVaGs1ASO64Ey0IANNVtHbSUYALsjxxbdAPahf9Vse9CtqroxDiRumY2-tROS4rsEK4RgiBDI0Uh0KyrHS2spn1_sTaTWaLtsNhjLp_Bn1-M_ifahN-K1lLxjnLgHdPgBh-TZhGtfWpyz-lBwxTUhxoJfJk0GQrPVm7GFKK6P49w6g6JK2OSatD0uqYNDwCrEKaRw</recordid><startdate>20190919</startdate><enddate>20190919</enddate><creator>Wang, Youliang</creator><creator>Zhu, Xuejing</creator><creator>Yuan, Shuguang</creator><creator>Wen, Si</creator><creator>Liu, Xuemei</creator><creator>Wang, Chang</creator><creator>Qu, Zhong</creator><creator>Li, Jun</creator><creator>Liu, Hong</creator><creator>Sun, Lin</creator><creator>Liu, Fuyou</creator><general>Frontiers Media S.A</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20190919</creationdate><title>TLR4/NF-κB Signaling Induces GSDMD-Related Pyroptosis in Tubular Cells in Diabetic Kidney Disease</title><author>Wang, Youliang ; Zhu, Xuejing ; Yuan, Shuguang ; Wen, Si ; Liu, Xuemei ; Wang, Chang ; Qu, Zhong ; Li, Jun ; Liu, Hong ; Sun, Lin ; Liu, Fuyou</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-284d00f1fce2692275b5deb5a743b28038d376ba13462f2f493433bc507f6f033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>diabetic kidney disease</topic><topic>Endocrinology</topic><topic>gasdermin-D</topic><topic>pyroptosis</topic><topic>Toll-like receptor-4</topic><topic>tubular injury</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Youliang</creatorcontrib><creatorcontrib>Zhu, Xuejing</creatorcontrib><creatorcontrib>Yuan, Shuguang</creatorcontrib><creatorcontrib>Wen, Si</creatorcontrib><creatorcontrib>Liu, Xuemei</creatorcontrib><creatorcontrib>Wang, Chang</creatorcontrib><creatorcontrib>Qu, Zhong</creatorcontrib><creatorcontrib>Li, Jun</creatorcontrib><creatorcontrib>Liu, Hong</creatorcontrib><creatorcontrib>Sun, Lin</creatorcontrib><creatorcontrib>Liu, Fuyou</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>Frontiers in endocrinology (Lausanne)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Youliang</au><au>Zhu, Xuejing</au><au>Yuan, Shuguang</au><au>Wen, Si</au><au>Liu, Xuemei</au><au>Wang, Chang</au><au>Qu, Zhong</au><au>Li, Jun</au><au>Liu, Hong</au><au>Sun, Lin</au><au>Liu, Fuyou</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TLR4/NF-κB Signaling Induces GSDMD-Related Pyroptosis in Tubular Cells in Diabetic Kidney Disease</atitle><jtitle>Frontiers in endocrinology (Lausanne)</jtitle><date>2019-09-19</date><risdate>2019</risdate><volume>10</volume><spage>603</spage><epage>603</epage><pages>603-603</pages><issn>1664-2392</issn><eissn>1664-2392</eissn><abstract>Gasdermin D (GSDMD) has been proven to be a key protein in the activation of pyroptosis. Pyroptosis of renal tubular epithelial cells contributes to the progression of tubular injury in kidney diseases. However, it remains elusive whether and how GSDMD is involved in the regulation of diabetic kidney disease (DKD). In this study, we found that tubular injury is accompanied by the up-regulation of Toll-like receptor 4 (TLR4) and GSDMD in patients with diabetic kidney disease. In addition, we discovered that the expressions of cleaved Caspase-1, active N-terminal fragments of GSDMD (GSDMD-NT), IL-18, and the secretion of IL-1β also increased in the kidneys of db/db mice. These changes were partially ameliorated following intraperitoneal injection of TAK-242, an inhibitor of TLR4. Similar results were observed in human tubular cells (HK-2) subjected to high-glucose (HG) conditions and treated with TAK-242 or parthenolide (inhibitor of NF-κB) by Western blot, Enzyme-linked immunosorbent assay (ELISA), and flow cytometry. These results indicated that TLR4/NF-κB signaling could induce GSDMD-mediated pyroptosis in tubular cells in DKD.</abstract><pub>Frontiers Media S.A</pub><pmid>31608008</pmid><doi>10.3389/fendo.2019.00603</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | diabetic kidney disease Endocrinology gasdermin-D pyroptosis Toll-like receptor-4 tubular injury |
title | TLR4/NF-κB Signaling Induces GSDMD-Related Pyroptosis in Tubular Cells in Diabetic Kidney Disease |
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