Increased renal expression of monocyte chemoattractant protein-1 and osteopontin in ADPKD in rats
Increased renal expression of monocyte chemoattractant protein-1 and osteopontin in ADPKD in rats. Human autosomal-dominant polycystic kidney disease (ADPKD) is variable in the rate of deterioration of renal function, with end-stage renal disease (ESRD) occurring in only approximately 50% of affecte...
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| Veröffentlicht in: | Kidney international 2001-12, Vol.60 (6), p.2087-2096 |
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| description | Increased renal expression of monocyte chemoattractant protein-1 and osteopontin in ADPKD in rats.
Human autosomal-dominant polycystic kidney disease (ADPKD) is variable in the rate of deterioration of renal function, with end-stage renal disease (ESRD) occurring in only approximately 50% of affected individuals. Evidence suggests that interstitial inflammation may be important in the development of ESRD in ADPKD. Han:SPRD rats manifest ADPKD that resembles the human disease. Homozygous cystic (Cy/Cy) rats develop rapidly progressive PKD and die near age 3 weeks. Heterozygous (Cy/+) females develop slowly progressive PKD without evidence of renal dysfunction until the second year of life, whereas heterozygous (Cy/+) males develop more aggressive PKD with renal failure beginning by 8 to 12 weeks of age.
To examine the relationship between proinflammatory chemoattractants and the development of interstitial inflammation and ultimately renal failure in ADPKD, we evaluated monocyte chemoattractant protein-1 (MCP-1) and osteopontin mRNAs and proteins in kidneys from Han:SRPD rats.
MCP-1 and osteopontin mRNAs, expressed at low levels in kidneys from normal (+/+) animals at all ages, were markedly elevated in kidneys from 3-week-old Cy/Cy animals. In kidneys from heterozygous (Cy/+) adults of either gender, MCP-1 and osteopontin mRNAs were more abundant than normal; MCP-1 mRNA was more abundant in Cy/+ males than in females. Thus, chemoattractant mRNA expression correlated with the development of renal failure in Cy/Cy and Cy/+ rats. Osteopontin mRNA, localized by in situ hybridization, was moderately expressed in the renal medulla of normal animals; however, this mRNA was expressed at very high levels in the cystic epithelia of Cy/+ and Cy/Cy animals. MCP-1 and osteopontin proteins, localized by immunohistochemistry, were weakly detected in +/+ kidneys but were densely expressed in Cy/Cy and in adult Cy/+ kidneys, primarily over cystic epithelium. Increased expression of chemoattractants was associated with the accumulation of ED-1 positive cells (macrophages) in the interstitium of cystic kidneys.
We suggest that proinflammatory chemoattractants have a role in the development of interstitial inflammation and renal failure in ADPKD. |
| doi_str_mv | 10.1046/j.1523-1755.2001.00065.x |
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Human autosomal-dominant polycystic kidney disease (ADPKD) is variable in the rate of deterioration of renal function, with end-stage renal disease (ESRD) occurring in only approximately 50% of affected individuals. Evidence suggests that interstitial inflammation may be important in the development of ESRD in ADPKD. Han:SPRD rats manifest ADPKD that resembles the human disease. Homozygous cystic (Cy/Cy) rats develop rapidly progressive PKD and die near age 3 weeks. Heterozygous (Cy/+) females develop slowly progressive PKD without evidence of renal dysfunction until the second year of life, whereas heterozygous (Cy/+) males develop more aggressive PKD with renal failure beginning by 8 to 12 weeks of age.
To examine the relationship between proinflammatory chemoattractants and the development of interstitial inflammation and ultimately renal failure in ADPKD, we evaluated monocyte chemoattractant protein-1 (MCP-1) and osteopontin mRNAs and proteins in kidneys from Han:SRPD rats.
MCP-1 and osteopontin mRNAs, expressed at low levels in kidneys from normal (+/+) animals at all ages, were markedly elevated in kidneys from 3-week-old Cy/Cy animals. In kidneys from heterozygous (Cy/+) adults of either gender, MCP-1 and osteopontin mRNAs were more abundant than normal; MCP-1 mRNA was more abundant in Cy/+ males than in females. Thus, chemoattractant mRNA expression correlated with the development of renal failure in Cy/Cy and Cy/+ rats. Osteopontin mRNA, localized by in situ hybridization, was moderately expressed in the renal medulla of normal animals; however, this mRNA was expressed at very high levels in the cystic epithelia of Cy/+ and Cy/Cy animals. MCP-1 and osteopontin proteins, localized by immunohistochemistry, were weakly detected in +/+ kidneys but were densely expressed in Cy/Cy and in adult Cy/+ kidneys, primarily over cystic epithelium. Increased expression of chemoattractants was associated with the accumulation of ED-1 positive cells (macrophages) in the interstitium of cystic kidneys.
We suggest that proinflammatory chemoattractants have a role in the development of interstitial inflammation and renal failure in ADPKD.</description><identifier>ISSN: 0085-2538</identifier><identifier>EISSN: 1523-1755</identifier><identifier>DOI: 10.1046/j.1523-1755.2001.00065.x</identifier><identifier>PMID: 11737583</identifier><identifier>CODEN: KDYIA5</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Animals ; autosomal-dominant PKD ; Biological and medical sciences ; Chemokine CCL2 - genetics ; Chemokine CCL2 - metabolism ; cysts ; Female ; fibrosis ; Heterozygote ; Immunohistochemistry ; In Situ Hybridization ; inherited disease ; interstitial inflammation ; Kidney - metabolism ; Kidney - pathology ; Kidneys ; Macrophages - pathology ; Male ; Medical sciences ; Nephrology. Urinary tract diseases ; Osteopontin ; Polycystic Kidney, Autosomal Dominant - metabolism ; Polycystic Kidney, Autosomal Dominant - pathology ; Rats ; Rats, Inbred Strains ; Reference Values ; renal failure ; RNA, Messenger - metabolism ; Sex Characteristics ; Sialoglycoproteins - genetics ; Sialoglycoproteins - metabolism ; Tumors of the urinary system</subject><ispartof>Kidney international, 2001-12, Vol.60 (6), p.2087-2096</ispartof><rights>2001 International Society of Nephrology</rights><rights>2002 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Dec 2001</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c565t-4b3a7b406ec0405cced7369773d2a32ed53c0790ac2ec8814dc46a4821c154053</citedby><cites>FETCH-LOGICAL-c565t-4b3a7b406ec0405cced7369773d2a32ed53c0790ac2ec8814dc46a4821c154053</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/210155464?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>315,781,785,27929,27930,64390,64392,64394,72474</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14141210$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11737583$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cowley, Benjamin D.</creatorcontrib><creatorcontrib>Ricardo, Sharon D.</creatorcontrib><creatorcontrib>Nagao, Shizuko</creatorcontrib><creatorcontrib>Diamond, Jonathan R.</creatorcontrib><title>Increased renal expression of monocyte chemoattractant protein-1 and osteopontin in ADPKD in rats</title><title>Kidney international</title><addtitle>Kidney Int</addtitle><description>Increased renal expression of monocyte chemoattractant protein-1 and osteopontin in ADPKD in rats.
Human autosomal-dominant polycystic kidney disease (ADPKD) is variable in the rate of deterioration of renal function, with end-stage renal disease (ESRD) occurring in only approximately 50% of affected individuals. Evidence suggests that interstitial inflammation may be important in the development of ESRD in ADPKD. Han:SPRD rats manifest ADPKD that resembles the human disease. Homozygous cystic (Cy/Cy) rats develop rapidly progressive PKD and die near age 3 weeks. Heterozygous (Cy/+) females develop slowly progressive PKD without evidence of renal dysfunction until the second year of life, whereas heterozygous (Cy/+) males develop more aggressive PKD with renal failure beginning by 8 to 12 weeks of age.
To examine the relationship between proinflammatory chemoattractants and the development of interstitial inflammation and ultimately renal failure in ADPKD, we evaluated monocyte chemoattractant protein-1 (MCP-1) and osteopontin mRNAs and proteins in kidneys from Han:SRPD rats.
MCP-1 and osteopontin mRNAs, expressed at low levels in kidneys from normal (+/+) animals at all ages, were markedly elevated in kidneys from 3-week-old Cy/Cy animals. In kidneys from heterozygous (Cy/+) adults of either gender, MCP-1 and osteopontin mRNAs were more abundant than normal; MCP-1 mRNA was more abundant in Cy/+ males than in females. Thus, chemoattractant mRNA expression correlated with the development of renal failure in Cy/Cy and Cy/+ rats. Osteopontin mRNA, localized by in situ hybridization, was moderately expressed in the renal medulla of normal animals; however, this mRNA was expressed at very high levels in the cystic epithelia of Cy/+ and Cy/Cy animals. MCP-1 and osteopontin proteins, localized by immunohistochemistry, were weakly detected in +/+ kidneys but were densely expressed in Cy/Cy and in adult Cy/+ kidneys, primarily over cystic epithelium. Increased expression of chemoattractants was associated with the accumulation of ED-1 positive cells (macrophages) in the interstitium of cystic kidneys.
We suggest that proinflammatory chemoattractants have a role in the development of interstitial inflammation and renal failure in ADPKD.</description><subject>Animals</subject><subject>autosomal-dominant PKD</subject><subject>Biological and medical sciences</subject><subject>Chemokine CCL2 - genetics</subject><subject>Chemokine CCL2 - metabolism</subject><subject>cysts</subject><subject>Female</subject><subject>fibrosis</subject><subject>Heterozygote</subject><subject>Immunohistochemistry</subject><subject>In Situ Hybridization</subject><subject>inherited disease</subject><subject>interstitial inflammation</subject><subject>Kidney - metabolism</subject><subject>Kidney - pathology</subject><subject>Kidneys</subject><subject>Macrophages - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Osteopontin</subject><subject>Polycystic Kidney, Autosomal Dominant - metabolism</subject><subject>Polycystic Kidney, Autosomal Dominant - pathology</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Reference Values</subject><subject>renal failure</subject><subject>RNA, Messenger - metabolism</subject><subject>Sex Characteristics</subject><subject>Sialoglycoproteins - genetics</subject><subject>Sialoglycoproteins - metabolism</subject><subject>Tumors of the urinary system</subject><issn>0085-2538</issn><issn>1523-1755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqFkV9rFDEUxYModlv9CEoQ9G3G_J3MPtbWarGgD_oc7mbuYpaZZE0ysv32ZtylBV8kgVy4v3s5OYcQylnLmere71quhWy40boVjPGWMdbp9vCErB4aT8mKsV43Qsv-jJznvKtQv5bsOTnj3Eije7kicBtcQsg40IQBRoqHfcKcfQw0bukUQ3T3Ban7iVOEUhK4AqHQfYoFfWg4hTDQmAvGfQzFB1rv5fW3L9dLkaDkF-TZFsaML0_vBflx8_H71efm7uun26vLu8bpTpdGbSSYjWIdOqaYdg4HI7u1MXIQIAUOWjpm1gycQNf3XA1OdaB6wR3XdUBekHfHvVXarxlzsZPPDscRAsY5WyOkErwTFXzzD7iLc6p_z1ZwxrVWnapQf4Rcijkn3Np98hOke8uZXTKwO7tYbRer7ZKB_ZuBPdTR16f982bC4XHwZHoF3p4AyA7GbYLgfH7kVD1VSeVeHbkAZU74ACi1Fp1eNH449rHa-ttjstl5DNU5n9AVO0T_f7V_ABoOrfY</recordid><startdate>20011201</startdate><enddate>20011201</enddate><creator>Cowley, Benjamin D.</creator><creator>Ricardo, Sharon D.</creator><creator>Nagao, Shizuko</creator><creator>Diamond, Jonathan R.</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>20011201</creationdate><title>Increased renal expression of monocyte chemoattractant protein-1 and osteopontin in ADPKD in rats</title><author>Cowley, Benjamin D. ; Ricardo, Sharon D. ; Nagao, Shizuko ; Diamond, Jonathan R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c565t-4b3a7b406ec0405cced7369773d2a32ed53c0790ac2ec8814dc46a4821c154053</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>autosomal-dominant PKD</topic><topic>Biological and medical sciences</topic><topic>Chemokine CCL2 - genetics</topic><topic>Chemokine CCL2 - metabolism</topic><topic>cysts</topic><topic>Female</topic><topic>fibrosis</topic><topic>Heterozygote</topic><topic>Immunohistochemistry</topic><topic>In Situ Hybridization</topic><topic>inherited disease</topic><topic>interstitial inflammation</topic><topic>Kidney - metabolism</topic><topic>Kidney - pathology</topic><topic>Kidneys</topic><topic>Macrophages - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Osteopontin</topic><topic>Polycystic Kidney, Autosomal Dominant - metabolism</topic><topic>Polycystic Kidney, Autosomal Dominant - pathology</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Reference Values</topic><topic>renal failure</topic><topic>RNA, Messenger - metabolism</topic><topic>Sex Characteristics</topic><topic>Sialoglycoproteins - genetics</topic><topic>Sialoglycoproteins - metabolism</topic><topic>Tumors of the urinary system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cowley, Benjamin D.</creatorcontrib><creatorcontrib>Ricardo, Sharon D.</creatorcontrib><creatorcontrib>Nagao, Shizuko</creatorcontrib><creatorcontrib>Diamond, Jonathan R.</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>Cowley, Benjamin D.</au><au>Ricardo, Sharon D.</au><au>Nagao, Shizuko</au><au>Diamond, Jonathan R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased renal expression of monocyte chemoattractant protein-1 and osteopontin in ADPKD in rats</atitle><jtitle>Kidney international</jtitle><addtitle>Kidney Int</addtitle><date>2001-12-01</date><risdate>2001</risdate><volume>60</volume><issue>6</issue><spage>2087</spage><epage>2096</epage><pages>2087-2096</pages><issn>0085-2538</issn><eissn>1523-1755</eissn><coden>KDYIA5</coden><abstract>Increased renal expression of monocyte chemoattractant protein-1 and osteopontin in ADPKD in rats.
Human autosomal-dominant polycystic kidney disease (ADPKD) is variable in the rate of deterioration of renal function, with end-stage renal disease (ESRD) occurring in only approximately 50% of affected individuals. Evidence suggests that interstitial inflammation may be important in the development of ESRD in ADPKD. Han:SPRD rats manifest ADPKD that resembles the human disease. Homozygous cystic (Cy/Cy) rats develop rapidly progressive PKD and die near age 3 weeks. Heterozygous (Cy/+) females develop slowly progressive PKD without evidence of renal dysfunction until the second year of life, whereas heterozygous (Cy/+) males develop more aggressive PKD with renal failure beginning by 8 to 12 weeks of age.
To examine the relationship between proinflammatory chemoattractants and the development of interstitial inflammation and ultimately renal failure in ADPKD, we evaluated monocyte chemoattractant protein-1 (MCP-1) and osteopontin mRNAs and proteins in kidneys from Han:SRPD rats.
MCP-1 and osteopontin mRNAs, expressed at low levels in kidneys from normal (+/+) animals at all ages, were markedly elevated in kidneys from 3-week-old Cy/Cy animals. In kidneys from heterozygous (Cy/+) adults of either gender, MCP-1 and osteopontin mRNAs were more abundant than normal; MCP-1 mRNA was more abundant in Cy/+ males than in females. Thus, chemoattractant mRNA expression correlated with the development of renal failure in Cy/Cy and Cy/+ rats. Osteopontin mRNA, localized by in situ hybridization, was moderately expressed in the renal medulla of normal animals; however, this mRNA was expressed at very high levels in the cystic epithelia of Cy/+ and Cy/Cy animals. MCP-1 and osteopontin proteins, localized by immunohistochemistry, were weakly detected in +/+ kidneys but were densely expressed in Cy/Cy and in adult Cy/+ kidneys, primarily over cystic epithelium. Increased expression of chemoattractants was associated with the accumulation of ED-1 positive cells (macrophages) in the interstitium of cystic kidneys.
We suggest that proinflammatory chemoattractants have a role in the development of interstitial inflammation and renal failure in ADPKD.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>11737583</pmid><doi>10.1046/j.1523-1755.2001.00065.x</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals autosomal-dominant PKD Biological and medical sciences Chemokine CCL2 - genetics Chemokine CCL2 - metabolism cysts Female fibrosis Heterozygote Immunohistochemistry In Situ Hybridization inherited disease interstitial inflammation Kidney - metabolism Kidney - pathology Kidneys Macrophages - pathology Male Medical sciences Nephrology. Urinary tract diseases Osteopontin Polycystic Kidney, Autosomal Dominant - metabolism Polycystic Kidney, Autosomal Dominant - pathology Rats Rats, Inbred Strains Reference Values renal failure RNA, Messenger - metabolism Sex Characteristics Sialoglycoproteins - genetics Sialoglycoproteins - metabolism Tumors of the urinary system |
| title | Increased renal expression of monocyte chemoattractant protein-1 and osteopontin in ADPKD in rats |
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