TGF-β/Smad3 Signaling Promotes Renal Fibrosis by Inhibiting miR-29
TGF-β/Smad3 signaling promotes fibrosis, but the development of therapeutic interventions involving this pathway will require the identification and ultimate targeting of downstream fibrosis-specific genes. In this study, using a microRNA microarray and real-time PCR, wild-type mice had reduced expr...
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| Veröffentlicht in: | Journal of the American Society of Nephrology 2011-08, Vol.22 (8), p.1462-1474 |
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| container_title | Journal of the American Society of Nephrology |
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| creator | WEI QIN CHUNG, Arthur C. K HUANG, Xiao R MENG, Xiao-Ming HUI, David S. C YU, Cheuk-Man SUNG, Joseph J. Y LAN, Hui Y |
| description | TGF-β/Smad3 signaling promotes fibrosis, but the development of therapeutic interventions involving this pathway will require the identification and ultimate targeting of downstream fibrosis-specific genes. In this study, using a microRNA microarray and real-time PCR, wild-type mice had reduced expression of miR-29 along with the development of progressive renal fibrosis in obstructive nephropathy. In contrast, Smad3 knockout mice had increased expression of miR-29 along with the absence of renal fibrosis in the same model of obstruction. In cultured fibroblasts and tubular epithelial cells, Smad3 mediated TGF-β(1)-induced downregulation of miR-29 by binding to the promoter of miR-29. Furthermore, miR-29 acted as a downstream inhibitor and therapeutic microRNA for TGF-β/Smad3-mediated fibrosis. In vitro, overexpression of miR-29b inhibited, but knockdown of miR-29 enhanced, TGF-β(1)-induced expression of collagens I and III by renal tubular cells. Ultrasound-mediated gene delivery of miR-29b either before or after established obstructive nephropathy blocked progressive renal fibrosis. In conclusion, miR-29 is a downstream inhibitor of TGF-β/Smad3-mediated fibrosis and may have therapeutic potential for diseases involving fibrosis. |
| doi_str_mv | 10.1681/ASN.2010121308 |
| format | Article |
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K ; HUANG, Xiao R ; MENG, Xiao-Ming ; HUI, David S. C ; YU, Cheuk-Man ; SUNG, Joseph J. Y ; LAN, Hui Y</creator><creatorcontrib>WEI QIN ; CHUNG, Arthur C. K ; HUANG, Xiao R ; MENG, Xiao-Ming ; HUI, David S. C ; YU, Cheuk-Man ; SUNG, Joseph J. Y ; LAN, Hui Y</creatorcontrib><description>TGF-β/Smad3 signaling promotes fibrosis, but the development of therapeutic interventions involving this pathway will require the identification and ultimate targeting of downstream fibrosis-specific genes. In this study, using a microRNA microarray and real-time PCR, wild-type mice had reduced expression of miR-29 along with the development of progressive renal fibrosis in obstructive nephropathy. In contrast, Smad3 knockout mice had increased expression of miR-29 along with the absence of renal fibrosis in the same model of obstruction. In cultured fibroblasts and tubular epithelial cells, Smad3 mediated TGF-β(1)-induced downregulation of miR-29 by binding to the promoter of miR-29. Furthermore, miR-29 acted as a downstream inhibitor and therapeutic microRNA for TGF-β/Smad3-mediated fibrosis. In vitro, overexpression of miR-29b inhibited, but knockdown of miR-29 enhanced, TGF-β(1)-induced expression of collagens I and III by renal tubular cells. Ultrasound-mediated gene delivery of miR-29b either before or after established obstructive nephropathy blocked progressive renal fibrosis. In conclusion, miR-29 is a downstream inhibitor of TGF-β/Smad3-mediated fibrosis and may have therapeutic potential for diseases involving fibrosis.</description><identifier>ISSN: 1046-6673</identifier><identifier>EISSN: 1533-3450</identifier><identifier>DOI: 10.1681/ASN.2010121308</identifier><identifier>PMID: 21784902</identifier><identifier>CODEN: JASNEU</identifier><language>eng</language><publisher>Washington, DC: American Society of Nephrology</publisher><subject>Animals ; Basic Research ; Biological and medical sciences ; Fibroblasts - cytology ; Fibrosis - pathology ; Kidney Diseases - pathology ; Kidneys ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; MicroRNAs - antagonists & inhibitors ; MicroRNAs - metabolism ; Nephrology. Urinary tract diseases ; Promoter Regions, Genetic ; Signal Transduction ; Smad3 Protein - metabolism ; Transforming Growth Factor beta - metabolism ; Treatment Outcome ; Urinary system involvement in other diseases. Miscellaneous</subject><ispartof>Journal of the American Society of Nephrology, 2011-08, Vol.22 (8), p.1462-1474</ispartof><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 by the American Society of Nephrology 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c464t-5287ca689faade06e8c272c7566208545876471d9f9d8ae4dff83aa250452a433</citedby><cites>FETCH-LOGICAL-c464t-5287ca689faade06e8c272c7566208545876471d9f9d8ae4dff83aa250452a433</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/PMC3148701/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148701/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24387615$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21784902$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>WEI QIN</creatorcontrib><creatorcontrib>CHUNG, Arthur C. K</creatorcontrib><creatorcontrib>HUANG, Xiao R</creatorcontrib><creatorcontrib>MENG, Xiao-Ming</creatorcontrib><creatorcontrib>HUI, David S. C</creatorcontrib><creatorcontrib>YU, Cheuk-Man</creatorcontrib><creatorcontrib>SUNG, Joseph J. Y</creatorcontrib><creatorcontrib>LAN, Hui Y</creatorcontrib><title>TGF-β/Smad3 Signaling Promotes Renal Fibrosis by Inhibiting miR-29</title><title>Journal of the American Society of Nephrology</title><addtitle>J Am Soc Nephrol</addtitle><description>TGF-β/Smad3 signaling promotes fibrosis, but the development of therapeutic interventions involving this pathway will require the identification and ultimate targeting of downstream fibrosis-specific genes. In this study, using a microRNA microarray and real-time PCR, wild-type mice had reduced expression of miR-29 along with the development of progressive renal fibrosis in obstructive nephropathy. In contrast, Smad3 knockout mice had increased expression of miR-29 along with the absence of renal fibrosis in the same model of obstruction. In cultured fibroblasts and tubular epithelial cells, Smad3 mediated TGF-β(1)-induced downregulation of miR-29 by binding to the promoter of miR-29. Furthermore, miR-29 acted as a downstream inhibitor and therapeutic microRNA for TGF-β/Smad3-mediated fibrosis. In vitro, overexpression of miR-29b inhibited, but knockdown of miR-29 enhanced, TGF-β(1)-induced expression of collagens I and III by renal tubular cells. Ultrasound-mediated gene delivery of miR-29b either before or after established obstructive nephropathy blocked progressive renal fibrosis. In conclusion, miR-29 is a downstream inhibitor of TGF-β/Smad3-mediated fibrosis and may have therapeutic potential for diseases involving fibrosis.</description><subject>Animals</subject><subject>Basic Research</subject><subject>Biological and medical sciences</subject><subject>Fibroblasts - cytology</subject><subject>Fibrosis - pathology</subject><subject>Kidney Diseases - pathology</subject><subject>Kidneys</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>MicroRNAs - antagonists & inhibitors</subject><subject>MicroRNAs - metabolism</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Promoter Regions, Genetic</subject><subject>Signal Transduction</subject><subject>Smad3 Protein - metabolism</subject><subject>Transforming Growth Factor beta - metabolism</subject><subject>Treatment Outcome</subject><subject>Urinary system involvement in other diseases. 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Y</creator><creator>LAN, Hui Y</creator><general>American Society of Nephrology</general><scope>IQODW</scope><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110801</creationdate><title>TGF-β/Smad3 Signaling Promotes Renal Fibrosis by Inhibiting miR-29</title><author>WEI QIN ; CHUNG, Arthur C. K ; HUANG, Xiao R ; MENG, Xiao-Ming ; HUI, David S. C ; YU, Cheuk-Man ; SUNG, Joseph J. Y ; LAN, Hui Y</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c464t-5287ca689faade06e8c272c7566208545876471d9f9d8ae4dff83aa250452a433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Basic Research</topic><topic>Biological and medical sciences</topic><topic>Fibroblasts - cytology</topic><topic>Fibrosis - pathology</topic><topic>Kidney Diseases - pathology</topic><topic>Kidneys</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>MicroRNAs - antagonists & inhibitors</topic><topic>MicroRNAs - metabolism</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Promoter Regions, Genetic</topic><topic>Signal Transduction</topic><topic>Smad3 Protein - metabolism</topic><topic>Transforming Growth Factor beta - metabolism</topic><topic>Treatment Outcome</topic><topic>Urinary system involvement in other diseases. Miscellaneous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>WEI QIN</creatorcontrib><creatorcontrib>CHUNG, Arthur C. K</creatorcontrib><creatorcontrib>HUANG, Xiao R</creatorcontrib><creatorcontrib>MENG, Xiao-Ming</creatorcontrib><creatorcontrib>HUI, David S. C</creatorcontrib><creatorcontrib>YU, Cheuk-Man</creatorcontrib><creatorcontrib>SUNG, Joseph J. Y</creatorcontrib><creatorcontrib>LAN, Hui Y</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of the American Society of Nephrology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>WEI QIN</au><au>CHUNG, Arthur C. K</au><au>HUANG, Xiao R</au><au>MENG, Xiao-Ming</au><au>HUI, David S. C</au><au>YU, Cheuk-Man</au><au>SUNG, Joseph J. Y</au><au>LAN, Hui Y</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TGF-β/Smad3 Signaling Promotes Renal Fibrosis by Inhibiting miR-29</atitle><jtitle>Journal of the American Society of Nephrology</jtitle><addtitle>J Am Soc Nephrol</addtitle><date>2011-08-01</date><risdate>2011</risdate><volume>22</volume><issue>8</issue><spage>1462</spage><epage>1474</epage><pages>1462-1474</pages><issn>1046-6673</issn><eissn>1533-3450</eissn><coden>JASNEU</coden><abstract>TGF-β/Smad3 signaling promotes fibrosis, but the development of therapeutic interventions involving this pathway will require the identification and ultimate targeting of downstream fibrosis-specific genes. In this study, using a microRNA microarray and real-time PCR, wild-type mice had reduced expression of miR-29 along with the development of progressive renal fibrosis in obstructive nephropathy. In contrast, Smad3 knockout mice had increased expression of miR-29 along with the absence of renal fibrosis in the same model of obstruction. In cultured fibroblasts and tubular epithelial cells, Smad3 mediated TGF-β(1)-induced downregulation of miR-29 by binding to the promoter of miR-29. Furthermore, miR-29 acted as a downstream inhibitor and therapeutic microRNA for TGF-β/Smad3-mediated fibrosis. In vitro, overexpression of miR-29b inhibited, but knockdown of miR-29 enhanced, TGF-β(1)-induced expression of collagens I and III by renal tubular cells. Ultrasound-mediated gene delivery of miR-29b either before or after established obstructive nephropathy blocked progressive renal fibrosis. In conclusion, miR-29 is a downstream inhibitor of TGF-β/Smad3-mediated fibrosis and may have therapeutic potential for diseases involving fibrosis.</abstract><cop>Washington, DC</cop><pub>American Society of Nephrology</pub><pmid>21784902</pmid><doi>10.1681/ASN.2010121308</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Basic Research Biological and medical sciences Fibroblasts - cytology Fibrosis - pathology Kidney Diseases - pathology Kidneys Male Medical sciences Mice Mice, Inbred C57BL Mice, Knockout MicroRNAs - antagonists & inhibitors MicroRNAs - metabolism Nephrology. Urinary tract diseases Promoter Regions, Genetic Signal Transduction Smad3 Protein - metabolism Transforming Growth Factor beta - metabolism Treatment Outcome Urinary system involvement in other diseases. Miscellaneous |
| title | TGF-β/Smad3 Signaling Promotes Renal Fibrosis by Inhibiting miR-29 |
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