Cis and trans regulatory elements in NPHS2 promoter: Implications in proteinuria and progression of renal diseases
Podocin (NPHS2) expression in podocytes is associated with variable degrees of proteinuria and progression to renal failure in different glomerular diseases that suggests different expression profiles in NPHS2 promoter. Three functional polymorphisms in NPHS2 promoter (-51T, −116T, and −535 insCTTTT...
Gespeichert in:
| Veröffentlicht in: | Kidney international 2006-10, Vol.70 (7), p.1332-1341 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1341 |
|---|---|
| container_issue | 7 |
| container_start_page | 1332 |
| container_title | Kidney international |
| container_volume | 70 |
| creator | Di Duca, M. Oleggini, R. Sanna-Cherchi, S. Pasquali, L. Di Donato, A. Parodi, S. Bertelli, R. Caridi, G. Frasca, G. Cerullo, G. Amoroso, A. Schena, F.P. Scolari, F. Ghiggeri, G.M. The European IgA Nephropathy Consortium |
| description | Podocin (NPHS2) expression in podocytes is associated with variable degrees of proteinuria and progression to renal failure in different glomerular diseases that suggests different expression profiles in NPHS2 promoter. Three functional polymorphisms in NPHS2 promoter (-51T, −116T, and −535 insCTTTTTT3) were found determining strong downregulation (-73, −59, and −82%, respectively) of the reporter gene expression when transfected in podocytes. Electrophoretic mobility shift assay experiments showed that all wild-type variants (-51G, −116C, and −535 insCTTTTTT2) formed specific DNA–protein complexes with podocyte nuclear extracts that were abolished by the presence of the rare forms (-51T, −116T, and −535 insCTTTTTT3). In the case of −51G, upstream stimulatory factor-1 (USF1) was identified as the specific trans element in accord to binding inhibition experiments and USF1 RNAi silencing. Haplotype analysis of 204 normal controls and 545 patients with renal diseases (308 immunoglobulin (Ig)A nephropathy and 237 focal segmental glomerulosclerosis) evidenced that −116/−51 and −535/P2OL formed two blocks in strong linkage disequilibrium in both normal and pathological cohorts. The high NPHS2 promoter profile −116C/−51G haplotype was more frequent in patients with IgA nephropathy (P−value=0.005) and was associated with a better clinical outcome in terms of proteinuria and creatinine levels. Overall our study describes functional variants of NPHS2 promoter and characterizes trans-acting elements that modulate podocin expression in the kidney. High producer NPHS2 promoter haplotypes seem protective in patients with chronic glomerular diseases. |
| doi_str_mv | 10.1038/sj.ki.5001767 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_68876545</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0085253815521315</els_id><sourcerecordid>1136754171</sourcerecordid><originalsourceid>FETCH-LOGICAL-c435t-ef6dbd5ea0e54f157097caa26f5b58538559d3923273b102d9878fa875fc3443</originalsourceid><addsrcrecordid>eNp1kc1r3DAUxEVpaTZpj70WUWhu3ujDsuTewpI0gdAUmrvQys9BG1ve6smF_PfVZg2BQk9imB_DaB4hnzhbcybNBe7WT2GtGOO60W_IiishK66VektWjBlVCSXNCTlF3LGiW8nekxPetAdhViRtAlIXO5qTi0gTPM6Dy1N6pjDACDEjDZH--HnzS9B9msYpQ_pGb8f9ELzLYYovfnEyhDin4F7Cin5MgFh8OvUlNbqBdgHBIeAH8q53A8LH5T0jD9dXD5ub6u7---3m8q7ytVS5gr7ptp0Cx0DVPVeatdo7J5pebZUpn1Kq7WQrpNByy5noWqNN74xWvZd1Lc_I-TG2lPk9A2Y7BvQwDC7CNKNtjNGNqlUBv_wD7qY5lcZoBWdcCMOaAlVHyKcJMUFv9ymMLj1bzuzhEBZ39inY5RCF_7yEztsRuld6Wb4AXxfAoXdDX-b3AV85U0jRHoL0kYMy1Z8AyaIPED10IYHPtpvCfyr8BUCMpHk</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>210122806</pqid></control><display><type>article</type><title>Cis and trans regulatory elements in NPHS2 promoter: Implications in proteinuria and progression of renal diseases</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>ProQuest Central UK/Ireland</source><source>Alma/SFX Local Collection</source><creator>Di Duca, M. ; Oleggini, R. ; Sanna-Cherchi, S. ; Pasquali, L. ; Di Donato, A. ; Parodi, S. ; Bertelli, R. ; Caridi, G. ; Frasca, G. ; Cerullo, G. ; Amoroso, A. ; Schena, F.P. ; Scolari, F. ; Ghiggeri, G.M. ; The European IgA Nephropathy Consortium</creator><creatorcontrib>Di Duca, M. ; Oleggini, R. ; Sanna-Cherchi, S. ; Pasquali, L. ; Di Donato, A. ; Parodi, S. ; Bertelli, R. ; Caridi, G. ; Frasca, G. ; Cerullo, G. ; Amoroso, A. ; Schena, F.P. ; Scolari, F. ; Ghiggeri, G.M. ; The European IgA Nephropathy Consortium ; European IgA Nephropathy Consortium</creatorcontrib><description>Podocin (NPHS2) expression in podocytes is associated with variable degrees of proteinuria and progression to renal failure in different glomerular diseases that suggests different expression profiles in NPHS2 promoter. Three functional polymorphisms in NPHS2 promoter (-51T, −116T, and −535 insCTTTTTT3) were found determining strong downregulation (-73, −59, and −82%, respectively) of the reporter gene expression when transfected in podocytes. Electrophoretic mobility shift assay experiments showed that all wild-type variants (-51G, −116C, and −535 insCTTTTTT2) formed specific DNA–protein complexes with podocyte nuclear extracts that were abolished by the presence of the rare forms (-51T, −116T, and −535 insCTTTTTT3). In the case of −51G, upstream stimulatory factor-1 (USF1) was identified as the specific trans element in accord to binding inhibition experiments and USF1 RNAi silencing. Haplotype analysis of 204 normal controls and 545 patients with renal diseases (308 immunoglobulin (Ig)A nephropathy and 237 focal segmental glomerulosclerosis) evidenced that −116/−51 and −535/P2OL formed two blocks in strong linkage disequilibrium in both normal and pathological cohorts. The high NPHS2 promoter profile −116C/−51G haplotype was more frequent in patients with IgA nephropathy (P−value=0.005) and was associated with a better clinical outcome in terms of proteinuria and creatinine levels. Overall our study describes functional variants of NPHS2 promoter and characterizes trans-acting elements that modulate podocin expression in the kidney. High producer NPHS2 promoter haplotypes seem protective in patients with chronic glomerular diseases.</description><identifier>ISSN: 0085-2538</identifier><identifier>EISSN: 1523-1755</identifier><identifier>DOI: 10.1038/sj.ki.5001767</identifier><identifier>PMID: 16900088</identifier><identifier>CODEN: KDYIA5</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Aged ; Animals ; Biological and medical sciences ; Cell Line ; Child ; Child, Preschool ; Chronic Disease ; Cohort Studies ; Creatinine - blood ; Data Interpretation, Statistical ; Disease Progression ; Female ; focal segmental glomerulosclerosis ; Follow-Up Studies ; Gene Expression Regulation ; Gene Frequency ; Genetic Variation ; Glomerulonephritis ; Glomerulonephritis, IGA - genetics ; Glomerulosclerosis, Focal Segmental - genetics ; haplotype analysis ; Haplotypes ; Humans ; IgA nephropathy ; Infant ; Intracellular Signaling Peptides and Proteins - genetics ; Kidney Diseases - genetics ; Luciferases - genetics ; Male ; Medical sciences ; Membrane Proteins - genetics ; Middle Aged ; Nephrology. Urinary tract diseases ; Nephropathies. Renovascular diseases. Renal failure ; Nephrotic Syndrome - genetics ; podocin expression ; Podocytes - metabolism ; Polymorphism, Single Nucleotide ; progression of renal diseases ; Promoter Regions, Genetic ; Proteinuria - genetics ; Sequence Analysis, DNA ; Time Factors ; trans-acting elements ; Urinary system involvement in other diseases. Miscellaneous ; Urinary tract. Prostate gland</subject><ispartof>Kidney international, 2006-10, Vol.70 (7), p.1332-1341</ispartof><rights>2006 International Society of Nephrology</rights><rights>2006 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Oct 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-ef6dbd5ea0e54f157097caa26f5b58538559d3923273b102d9878fa875fc3443</citedby><cites>FETCH-LOGICAL-c435t-ef6dbd5ea0e54f157097caa26f5b58538559d3923273b102d9878fa875fc3443</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/210122806?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18169297$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16900088$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Di Duca, M.</creatorcontrib><creatorcontrib>Oleggini, R.</creatorcontrib><creatorcontrib>Sanna-Cherchi, S.</creatorcontrib><creatorcontrib>Pasquali, L.</creatorcontrib><creatorcontrib>Di Donato, A.</creatorcontrib><creatorcontrib>Parodi, S.</creatorcontrib><creatorcontrib>Bertelli, R.</creatorcontrib><creatorcontrib>Caridi, G.</creatorcontrib><creatorcontrib>Frasca, G.</creatorcontrib><creatorcontrib>Cerullo, G.</creatorcontrib><creatorcontrib>Amoroso, A.</creatorcontrib><creatorcontrib>Schena, F.P.</creatorcontrib><creatorcontrib>Scolari, F.</creatorcontrib><creatorcontrib>Ghiggeri, G.M.</creatorcontrib><creatorcontrib>The European IgA Nephropathy Consortium</creatorcontrib><creatorcontrib>European IgA Nephropathy Consortium</creatorcontrib><title>Cis and trans regulatory elements in NPHS2 promoter: Implications in proteinuria and progression of renal diseases</title><title>Kidney international</title><addtitle>Kidney Int</addtitle><description>Podocin (NPHS2) expression in podocytes is associated with variable degrees of proteinuria and progression to renal failure in different glomerular diseases that suggests different expression profiles in NPHS2 promoter. Three functional polymorphisms in NPHS2 promoter (-51T, −116T, and −535 insCTTTTTT3) were found determining strong downregulation (-73, −59, and −82%, respectively) of the reporter gene expression when transfected in podocytes. Electrophoretic mobility shift assay experiments showed that all wild-type variants (-51G, −116C, and −535 insCTTTTTT2) formed specific DNA–protein complexes with podocyte nuclear extracts that were abolished by the presence of the rare forms (-51T, −116T, and −535 insCTTTTTT3). In the case of −51G, upstream stimulatory factor-1 (USF1) was identified as the specific trans element in accord to binding inhibition experiments and USF1 RNAi silencing. Haplotype analysis of 204 normal controls and 545 patients with renal diseases (308 immunoglobulin (Ig)A nephropathy and 237 focal segmental glomerulosclerosis) evidenced that −116/−51 and −535/P2OL formed two blocks in strong linkage disequilibrium in both normal and pathological cohorts. The high NPHS2 promoter profile −116C/−51G haplotype was more frequent in patients with IgA nephropathy (P−value=0.005) and was associated with a better clinical outcome in terms of proteinuria and creatinine levels. Overall our study describes functional variants of NPHS2 promoter and characterizes trans-acting elements that modulate podocin expression in the kidney. High producer NPHS2 promoter haplotypes seem protective in patients with chronic glomerular diseases.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Chronic Disease</subject><subject>Cohort Studies</subject><subject>Creatinine - blood</subject><subject>Data Interpretation, Statistical</subject><subject>Disease Progression</subject><subject>Female</subject><subject>focal segmental glomerulosclerosis</subject><subject>Follow-Up Studies</subject><subject>Gene Expression Regulation</subject><subject>Gene Frequency</subject><subject>Genetic Variation</subject><subject>Glomerulonephritis</subject><subject>Glomerulonephritis, IGA - genetics</subject><subject>Glomerulosclerosis, Focal Segmental - genetics</subject><subject>haplotype analysis</subject><subject>Haplotypes</subject><subject>Humans</subject><subject>IgA nephropathy</subject><subject>Infant</subject><subject>Intracellular Signaling Peptides and Proteins - genetics</subject><subject>Kidney Diseases - genetics</subject><subject>Luciferases - genetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membrane Proteins - genetics</subject><subject>Middle Aged</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Nephropathies. Renovascular diseases. Renal failure</subject><subject>Nephrotic Syndrome - genetics</subject><subject>podocin expression</subject><subject>Podocytes - metabolism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>progression of renal diseases</subject><subject>Promoter Regions, Genetic</subject><subject>Proteinuria - genetics</subject><subject>Sequence Analysis, DNA</subject><subject>Time Factors</subject><subject>trans-acting elements</subject><subject>Urinary system involvement in other diseases. Miscellaneous</subject><subject>Urinary tract. Prostate gland</subject><issn>0085-2538</issn><issn>1523-1755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kc1r3DAUxEVpaTZpj70WUWhu3ujDsuTewpI0gdAUmrvQys9BG1ve6smF_PfVZg2BQk9imB_DaB4hnzhbcybNBe7WT2GtGOO60W_IiishK66VektWjBlVCSXNCTlF3LGiW8nekxPetAdhViRtAlIXO5qTi0gTPM6Dy1N6pjDACDEjDZH--HnzS9B9msYpQ_pGb8f9ELzLYYovfnEyhDin4F7Cin5MgFh8OvUlNbqBdgHBIeAH8q53A8LH5T0jD9dXD5ub6u7---3m8q7ytVS5gr7ptp0Cx0DVPVeatdo7J5pebZUpn1Kq7WQrpNByy5noWqNN74xWvZd1Lc_I-TG2lPk9A2Y7BvQwDC7CNKNtjNGNqlUBv_wD7qY5lcZoBWdcCMOaAlVHyKcJMUFv9ymMLj1bzuzhEBZ39inY5RCF_7yEztsRuld6Wb4AXxfAoXdDX-b3AV85U0jRHoL0kYMy1Z8AyaIPED10IYHPtpvCfyr8BUCMpHk</recordid><startdate>20061001</startdate><enddate>20061001</enddate><creator>Di Duca, M.</creator><creator>Oleggini, R.</creator><creator>Sanna-Cherchi, S.</creator><creator>Pasquali, L.</creator><creator>Di Donato, A.</creator><creator>Parodi, S.</creator><creator>Bertelli, R.</creator><creator>Caridi, G.</creator><creator>Frasca, G.</creator><creator>Cerullo, G.</creator><creator>Amoroso, A.</creator><creator>Schena, F.P.</creator><creator>Scolari, F.</creator><creator>Ghiggeri, G.M.</creator><creator>The European IgA Nephropathy Consortium</creator><general>Elsevier Inc</general><general>Nature Publishing</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><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>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20061001</creationdate><title>Cis and trans regulatory elements in NPHS2 promoter: Implications in proteinuria and progression of renal diseases</title><author>Di Duca, M. ; Oleggini, R. ; Sanna-Cherchi, S. ; Pasquali, L. ; Di Donato, A. ; Parodi, S. ; Bertelli, R. ; Caridi, G. ; Frasca, G. ; Cerullo, G. ; Amoroso, A. ; Schena, F.P. ; Scolari, F. ; Ghiggeri, G.M. ; The European IgA Nephropathy Consortium</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c435t-ef6dbd5ea0e54f157097caa26f5b58538559d3923273b102d9878fa875fc3443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Chronic Disease</topic><topic>Cohort Studies</topic><topic>Creatinine - blood</topic><topic>Data Interpretation, Statistical</topic><topic>Disease Progression</topic><topic>Female</topic><topic>focal segmental glomerulosclerosis</topic><topic>Follow-Up Studies</topic><topic>Gene Expression Regulation</topic><topic>Gene Frequency</topic><topic>Genetic Variation</topic><topic>Glomerulonephritis</topic><topic>Glomerulonephritis, IGA - genetics</topic><topic>Glomerulosclerosis, Focal Segmental - genetics</topic><topic>haplotype analysis</topic><topic>Haplotypes</topic><topic>Humans</topic><topic>IgA nephropathy</topic><topic>Infant</topic><topic>Intracellular Signaling Peptides and Proteins - genetics</topic><topic>Kidney Diseases - genetics</topic><topic>Luciferases - genetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Membrane Proteins - genetics</topic><topic>Middle Aged</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Nephropathies. Renovascular diseases. Renal failure</topic><topic>Nephrotic Syndrome - genetics</topic><topic>podocin expression</topic><topic>Podocytes - metabolism</topic><topic>Polymorphism, Single Nucleotide</topic><topic>progression of renal diseases</topic><topic>Promoter Regions, Genetic</topic><topic>Proteinuria - genetics</topic><topic>Sequence Analysis, DNA</topic><topic>Time Factors</topic><topic>trans-acting elements</topic><topic>Urinary system involvement in other diseases. Miscellaneous</topic><topic>Urinary tract. Prostate gland</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Di Duca, M.</creatorcontrib><creatorcontrib>Oleggini, R.</creatorcontrib><creatorcontrib>Sanna-Cherchi, S.</creatorcontrib><creatorcontrib>Pasquali, L.</creatorcontrib><creatorcontrib>Di Donato, A.</creatorcontrib><creatorcontrib>Parodi, S.</creatorcontrib><creatorcontrib>Bertelli, R.</creatorcontrib><creatorcontrib>Caridi, G.</creatorcontrib><creatorcontrib>Frasca, G.</creatorcontrib><creatorcontrib>Cerullo, G.</creatorcontrib><creatorcontrib>Amoroso, A.</creatorcontrib><creatorcontrib>Schena, F.P.</creatorcontrib><creatorcontrib>Scolari, F.</creatorcontrib><creatorcontrib>Ghiggeri, G.M.</creatorcontrib><creatorcontrib>The European IgA Nephropathy Consortium</creatorcontrib><creatorcontrib>European IgA Nephropathy Consortium</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</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>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>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</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><jtitle>Kidney international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Di Duca, M.</au><au>Oleggini, R.</au><au>Sanna-Cherchi, S.</au><au>Pasquali, L.</au><au>Di Donato, A.</au><au>Parodi, S.</au><au>Bertelli, R.</au><au>Caridi, G.</au><au>Frasca, G.</au><au>Cerullo, G.</au><au>Amoroso, A.</au><au>Schena, F.P.</au><au>Scolari, F.</au><au>Ghiggeri, G.M.</au><au>The European IgA Nephropathy Consortium</au><aucorp>European IgA Nephropathy Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cis and trans regulatory elements in NPHS2 promoter: Implications in proteinuria and progression of renal diseases</atitle><jtitle>Kidney international</jtitle><addtitle>Kidney Int</addtitle><date>2006-10-01</date><risdate>2006</risdate><volume>70</volume><issue>7</issue><spage>1332</spage><epage>1341</epage><pages>1332-1341</pages><issn>0085-2538</issn><eissn>1523-1755</eissn><coden>KDYIA5</coden><abstract>Podocin (NPHS2) expression in podocytes is associated with variable degrees of proteinuria and progression to renal failure in different glomerular diseases that suggests different expression profiles in NPHS2 promoter. Three functional polymorphisms in NPHS2 promoter (-51T, −116T, and −535 insCTTTTTT3) were found determining strong downregulation (-73, −59, and −82%, respectively) of the reporter gene expression when transfected in podocytes. Electrophoretic mobility shift assay experiments showed that all wild-type variants (-51G, −116C, and −535 insCTTTTTT2) formed specific DNA–protein complexes with podocyte nuclear extracts that were abolished by the presence of the rare forms (-51T, −116T, and −535 insCTTTTTT3). In the case of −51G, upstream stimulatory factor-1 (USF1) was identified as the specific trans element in accord to binding inhibition experiments and USF1 RNAi silencing. Haplotype analysis of 204 normal controls and 545 patients with renal diseases (308 immunoglobulin (Ig)A nephropathy and 237 focal segmental glomerulosclerosis) evidenced that −116/−51 and −535/P2OL formed two blocks in strong linkage disequilibrium in both normal and pathological cohorts. The high NPHS2 promoter profile −116C/−51G haplotype was more frequent in patients with IgA nephropathy (P−value=0.005) and was associated with a better clinical outcome in terms of proteinuria and creatinine levels. Overall our study describes functional variants of NPHS2 promoter and characterizes trans-acting elements that modulate podocin expression in the kidney. High producer NPHS2 promoter haplotypes seem protective in patients with chronic glomerular diseases.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>16900088</pmid><doi>10.1038/sj.ki.5001767</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0085-2538 |
| ispartof | Kidney international, 2006-10, Vol.70 (7), p.1332-1341 |
| issn | 0085-2538 1523-1755 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68876545 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; ProQuest Central UK/Ireland; Alma/SFX Local Collection |
| subjects | Adolescent Adult Aged Animals Biological and medical sciences Cell Line Child Child, Preschool Chronic Disease Cohort Studies Creatinine - blood Data Interpretation, Statistical Disease Progression Female focal segmental glomerulosclerosis Follow-Up Studies Gene Expression Regulation Gene Frequency Genetic Variation Glomerulonephritis Glomerulonephritis, IGA - genetics Glomerulosclerosis, Focal Segmental - genetics haplotype analysis Haplotypes Humans IgA nephropathy Infant Intracellular Signaling Peptides and Proteins - genetics Kidney Diseases - genetics Luciferases - genetics Male Medical sciences Membrane Proteins - genetics Middle Aged Nephrology. Urinary tract diseases Nephropathies. Renovascular diseases. Renal failure Nephrotic Syndrome - genetics podocin expression Podocytes - metabolism Polymorphism, Single Nucleotide progression of renal diseases Promoter Regions, Genetic Proteinuria - genetics Sequence Analysis, DNA Time Factors trans-acting elements Urinary system involvement in other diseases. Miscellaneous Urinary tract. Prostate gland |
| title | Cis and trans regulatory elements in NPHS2 promoter: Implications in proteinuria and progression of renal diseases |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-21T05%3A21%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cis%20and%20trans%20regulatory%20elements%20in%20NPHS2%20promoter:%20Implications%20in%20proteinuria%20and%20progression%20of%20renal%20diseases&rft.jtitle=Kidney%20international&rft.au=Di%20Duca,%20M.&rft.aucorp=European%20IgA%20Nephropathy%20Consortium&rft.date=2006-10-01&rft.volume=70&rft.issue=7&rft.spage=1332&rft.epage=1341&rft.pages=1332-1341&rft.issn=0085-2538&rft.eissn=1523-1755&rft.coden=KDYIA5&rft_id=info:doi/10.1038/sj.ki.5001767&rft_dat=%3Cproquest_cross%3E1136754171%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=210122806&rft_id=info:pmid/16900088&rft_els_id=S0085253815521315&rfr_iscdi=true |