Role of glomerular ultrafiltration of growth factors in progressive interstitial fibrosis in diabetic nephropathy
Role of glomerular ultrafiltration of growth factors in progressive interstitial fibrosis in diabetic nephropathy. The present in vivo and in vitro experiments were performed to test the hypothesis that in rats with glomerular proteinuria, the bioactive growth factors transforming growth factor-β (T...
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| description | Role of glomerular ultrafiltration of growth factors in progressive interstitial fibrosis in diabetic nephropathy.
The present in vivo and in vitro experiments were performed to test the hypothesis that in rats with glomerular proteinuria, the bioactive growth factors transforming growth factor-β (TGF-β) and hepatocyte growth factor (HGF) are ultrafiltered into tubular fluid, can interact with respective receptors in apical tubular cell membranes, increase the expression and basolateral secretion of C-C-chemokines, which interact with cells in the renal interstitium and indirectly cause myofibroblasts to increase the expression of extracellular matrix proteins.
HGF and TGF-β were measured by Western blot and bioassay in glomerular ultrafiltrate that was collected by nephron micropuncture from rats with diabetic nephropathy and control rats. Proximal tubular and collecting duct cells were incubated with diluted proximal tubular fluid or recombinant human HGF (rhHGF) or rhTGF-β and expression of C-C-chemokines was measured by RT-PCR and ELISA. Interactions of tubular cell chemokines with macrophages and indirectly with myofibroblasts were also examined using cell culture models.
In rats with glomerular proteinuria due to diabetic nephropathy mature, bioactive HGF as well as active and latent TGF-β were detected in early proximal tubular fluid. Specific HGF-and TGF-β type II receptors were expressed in apical tubular membranes more in diabetic compared to control rats. Incubation of cultured mouse proximal tubular cells (mPTC) or medullary collecting duct cells (mIMCD-3) with diabetic rat proximal tubular fluid increased MCP-1 and RANTES mRNA levels as well as secreted peptide up to threefold. In contrast, high glucose (450 mg/dL), bovine serum albumin (BSA) or rat albumin (each at 100 μg/mL) or 10 nmol/L insulin-like growth factor-I (IGF-I; which was also present in glomerular ultrafiltrate in rats with diabetic nephropathy) did not affect expression of these chemokines. Recombinant human TGF-β as well as rhHGF each increased MCP-1 and RANTES mRNA as well as peptide levels several-fold. In cultured macrophages MCP-1 raised the secretion of TGF-β, which in turn increased the expression of collagen type I and III as well as fibronectin in renal interstitial myofibroblasts about 2.5 to 4-fold.
Proteinuria-induced progressive renal interstitial fibrosis may be caused by glomerular ultrafiltration of high molecular weight bioactive growth factors, HGF and TGF-β, |
| doi_str_mv | 10.1046/j.1523-1755.2000.00928.x |
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The present in vivo and in vitro experiments were performed to test the hypothesis that in rats with glomerular proteinuria, the bioactive growth factors transforming growth factor-β (TGF-β) and hepatocyte growth factor (HGF) are ultrafiltered into tubular fluid, can interact with respective receptors in apical tubular cell membranes, increase the expression and basolateral secretion of C-C-chemokines, which interact with cells in the renal interstitium and indirectly cause myofibroblasts to increase the expression of extracellular matrix proteins.
HGF and TGF-β were measured by Western blot and bioassay in glomerular ultrafiltrate that was collected by nephron micropuncture from rats with diabetic nephropathy and control rats. Proximal tubular and collecting duct cells were incubated with diluted proximal tubular fluid or recombinant human HGF (rhHGF) or rhTGF-β and expression of C-C-chemokines was measured by RT-PCR and ELISA. Interactions of tubular cell chemokines with macrophages and indirectly with myofibroblasts were also examined using cell culture models.
In rats with glomerular proteinuria due to diabetic nephropathy mature, bioactive HGF as well as active and latent TGF-β were detected in early proximal tubular fluid. Specific HGF-and TGF-β type II receptors were expressed in apical tubular membranes more in diabetic compared to control rats. Incubation of cultured mouse proximal tubular cells (mPTC) or medullary collecting duct cells (mIMCD-3) with diabetic rat proximal tubular fluid increased MCP-1 and RANTES mRNA levels as well as secreted peptide up to threefold. In contrast, high glucose (450 mg/dL), bovine serum albumin (BSA) or rat albumin (each at 100 μg/mL) or 10 nmol/L insulin-like growth factor-I (IGF-I; which was also present in glomerular ultrafiltrate in rats with diabetic nephropathy) did not affect expression of these chemokines. Recombinant human TGF-β as well as rhHGF each increased MCP-1 and RANTES mRNA as well as peptide levels several-fold. In cultured macrophages MCP-1 raised the secretion of TGF-β, which in turn increased the expression of collagen type I and III as well as fibronectin in renal interstitial myofibroblasts about 2.5 to 4-fold.
Proteinuria-induced progressive renal interstitial fibrosis may be caused by glomerular ultrafiltration of high molecular weight bioactive growth factors, HGF and TGF-β, which “activate” tubular cells through apical membranes. These apical signals are translated into basolateral events that are recognized by cells in the interstitium, such as the basolateral secretion of the C-C-chemokines MCP-1 and RANTES, which may (via macrophages) stimulate interstitial myofibroblasts, and thus lead to accumulation of extracellular matrix proteins and progressive interstitial fibrosis.</description><identifier>ISSN: 0085-2538</identifier><identifier>EISSN: 1523-1755</identifier><identifier>DOI: 10.1046/j.1523-1755.2000.00928.x</identifier><identifier>PMID: 10720953</identifier><identifier>CODEN: KDYIA5</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Animals ; Associated diseases and complications ; Biological and medical sciences ; Body Fluids - metabolism ; Chemokine CCL2 - metabolism ; Chemokine CCL5 - metabolism ; Diabetes. Impaired glucose tolerance ; Diabetic Nephropathies - metabolism ; Diabetic Nephropathies - pathology ; diabetic nephropathy ; Disease Progression ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Extracellular Matrix Proteins - metabolism ; fibronectin ; Fibrosis - metabolism ; Glomerulonephritis ; hepatocyte growth factor ; Hepatocyte Growth Factor - metabolism ; Humans ; Kidney - cytology ; Kidney - metabolism ; Kidney Glomerulus - metabolism ; Kidney Tubules, Proximal - metabolism ; MCP-1 ; Medical sciences ; Mice ; Nephrology. Urinary tract diseases ; Nephropathies. Renovascular diseases. Renal failure ; proteinuria ; Proto-Oncogene Proteins c-met - metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Transforming Growth Factor beta - metabolism ; TGF-β ; Transforming Growth Factor beta - metabolism</subject><ispartof>Kidney international, 2000-03, Vol.57 (3), p.1002-1014</ispartof><rights>2000 International Society of Nephrology</rights><rights>2000 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Mar 2000</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c542t-89a35620016b972b0485b94c6fb8b8fc6bd651303d187550871f622d4770c0eb3</citedby><cites>FETCH-LOGICAL-c542t-89a35620016b972b0485b94c6fb8b8fc6bd651303d187550871f622d4770c0eb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>309,310,314,776,780,785,786,23909,23910,25118,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1282892$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10720953$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Shi-Nong</creatorcontrib><creatorcontrib>Lapage, Janine</creatorcontrib><creatorcontrib>Hirschberg, Raimund</creatorcontrib><title>Role of glomerular ultrafiltration of growth factors in progressive interstitial fibrosis in diabetic nephropathy</title><title>Kidney international</title><addtitle>Kidney Int</addtitle><description>Role of glomerular ultrafiltration of growth factors in progressive interstitial fibrosis in diabetic nephropathy.
The present in vivo and in vitro experiments were performed to test the hypothesis that in rats with glomerular proteinuria, the bioactive growth factors transforming growth factor-β (TGF-β) and hepatocyte growth factor (HGF) are ultrafiltered into tubular fluid, can interact with respective receptors in apical tubular cell membranes, increase the expression and basolateral secretion of C-C-chemokines, which interact with cells in the renal interstitium and indirectly cause myofibroblasts to increase the expression of extracellular matrix proteins.
HGF and TGF-β were measured by Western blot and bioassay in glomerular ultrafiltrate that was collected by nephron micropuncture from rats with diabetic nephropathy and control rats. Proximal tubular and collecting duct cells were incubated with diluted proximal tubular fluid or recombinant human HGF (rhHGF) or rhTGF-β and expression of C-C-chemokines was measured by RT-PCR and ELISA. Interactions of tubular cell chemokines with macrophages and indirectly with myofibroblasts were also examined using cell culture models.
In rats with glomerular proteinuria due to diabetic nephropathy mature, bioactive HGF as well as active and latent TGF-β were detected in early proximal tubular fluid. Specific HGF-and TGF-β type II receptors were expressed in apical tubular membranes more in diabetic compared to control rats. Incubation of cultured mouse proximal tubular cells (mPTC) or medullary collecting duct cells (mIMCD-3) with diabetic rat proximal tubular fluid increased MCP-1 and RANTES mRNA levels as well as secreted peptide up to threefold. In contrast, high glucose (450 mg/dL), bovine serum albumin (BSA) or rat albumin (each at 100 μg/mL) or 10 nmol/L insulin-like growth factor-I (IGF-I; which was also present in glomerular ultrafiltrate in rats with diabetic nephropathy) did not affect expression of these chemokines. Recombinant human TGF-β as well as rhHGF each increased MCP-1 and RANTES mRNA as well as peptide levels several-fold. In cultured macrophages MCP-1 raised the secretion of TGF-β, which in turn increased the expression of collagen type I and III as well as fibronectin in renal interstitial myofibroblasts about 2.5 to 4-fold.
Proteinuria-induced progressive renal interstitial fibrosis may be caused by glomerular ultrafiltration of high molecular weight bioactive growth factors, HGF and TGF-β, which “activate” tubular cells through apical membranes. These apical signals are translated into basolateral events that are recognized by cells in the interstitium, such as the basolateral secretion of the C-C-chemokines MCP-1 and RANTES, which may (via macrophages) stimulate interstitial myofibroblasts, and thus lead to accumulation of extracellular matrix proteins and progressive interstitial fibrosis.</description><subject>Animals</subject><subject>Associated diseases and complications</subject><subject>Biological and medical sciences</subject><subject>Body Fluids - metabolism</subject><subject>Chemokine CCL2 - metabolism</subject><subject>Chemokine CCL5 - metabolism</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Diabetic Nephropathies - metabolism</subject><subject>Diabetic Nephropathies - pathology</subject><subject>diabetic nephropathy</subject><subject>Disease Progression</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Extracellular Matrix Proteins - metabolism</subject><subject>fibronectin</subject><subject>Fibrosis - metabolism</subject><subject>Glomerulonephritis</subject><subject>hepatocyte growth factor</subject><subject>Hepatocyte Growth Factor - metabolism</subject><subject>Humans</subject><subject>Kidney - cytology</subject><subject>Kidney - metabolism</subject><subject>Kidney Glomerulus - metabolism</subject><subject>Kidney Tubules, Proximal - metabolism</subject><subject>MCP-1</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Nephropathies. Renovascular diseases. Renal failure</subject><subject>proteinuria</subject><subject>Proto-Oncogene Proteins c-met - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Transforming Growth Factor beta - metabolism</subject><subject>TGF-β</subject><subject>Transforming Growth Factor beta - metabolism</subject><issn>0085-2538</issn><issn>1523-1755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkU-LFDEQxYMo7rj6FaQR8dZtJd3pTh918R8sCKLnkKQrOxkyndkkve5-e9Mzg4oXLylC_aqo9x4hFYWGQte_3TWUs7amA-cNA4AGYGSiuX9ENr8bj8kGQPCa8VZckGcp7QooxhaekgsKA4ORtxty-y14rIKtbnzYY1y8itXic1TWrW92YT52Y_iZt5VVJoeYKjdXhxhuIqbk7rB8M8aUXXbKV9bpGJI7QpNTGrMz1YyHbQwHlbcPz8kTq3zCF-d6SX58_PD96nN9_fXTl6t317XhHcu1GFXL-yKO9nocmIZOcD12prdaaGFNr6ee0xbaiYqiFsRAbc_Y1A0DGEDdXpI3p73l0tsFU5Z7lwx6r2YMS5IDjCNwPhTw1T_gLixxLrdJRoGC6HhbIHGCTBGXIlp5iG6v4oOkINdM5E6u1svVerlmIo-ZyPsy-vK8f9F7nP4aPIVQgNdnQCWjvI1qNi794ZhgYmQFe3_CsLh25zDKZBzOBicX0WQ5Bff_Y34BzAKrVA</recordid><startdate>20000301</startdate><enddate>20000301</enddate><creator>Wang, Shi-Nong</creator><creator>Lapage, Janine</creator><creator>Hirschberg, Raimund</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>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20000301</creationdate><title>Role of glomerular ultrafiltration of growth factors in progressive interstitial fibrosis in diabetic nephropathy</title><author>Wang, Shi-Nong ; Lapage, Janine ; Hirschberg, Raimund</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c542t-89a35620016b972b0485b94c6fb8b8fc6bd651303d187550871f622d4770c0eb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Animals</topic><topic>Associated diseases and complications</topic><topic>Biological and medical sciences</topic><topic>Body Fluids - metabolism</topic><topic>Chemokine CCL2 - metabolism</topic><topic>Chemokine CCL5 - metabolism</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Diabetic Nephropathies - metabolism</topic><topic>Diabetic Nephropathies - pathology</topic><topic>diabetic nephropathy</topic><topic>Disease Progression</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Extracellular Matrix Proteins - metabolism</topic><topic>fibronectin</topic><topic>Fibrosis - metabolism</topic><topic>Glomerulonephritis</topic><topic>hepatocyte growth factor</topic><topic>Hepatocyte Growth Factor - metabolism</topic><topic>Humans</topic><topic>Kidney - cytology</topic><topic>Kidney - metabolism</topic><topic>Kidney Glomerulus - metabolism</topic><topic>Kidney Tubules, Proximal - metabolism</topic><topic>MCP-1</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Nephropathies. Renovascular diseases. Renal failure</topic><topic>proteinuria</topic><topic>Proto-Oncogene Proteins c-met - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Transforming Growth Factor beta - metabolism</topic><topic>TGF-β</topic><topic>Transforming Growth Factor beta - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Shi-Nong</creatorcontrib><creatorcontrib>Lapage, Janine</creatorcontrib><creatorcontrib>Hirschberg, Raimund</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 Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</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>Wang, Shi-Nong</au><au>Lapage, Janine</au><au>Hirschberg, Raimund</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of glomerular ultrafiltration of growth factors in progressive interstitial fibrosis in diabetic nephropathy</atitle><jtitle>Kidney international</jtitle><addtitle>Kidney Int</addtitle><date>2000-03-01</date><risdate>2000</risdate><volume>57</volume><issue>3</issue><spage>1002</spage><epage>1014</epage><pages>1002-1014</pages><issn>0085-2538</issn><eissn>1523-1755</eissn><coden>KDYIA5</coden><abstract>Role of glomerular ultrafiltration of growth factors in progressive interstitial fibrosis in diabetic nephropathy.
The present in vivo and in vitro experiments were performed to test the hypothesis that in rats with glomerular proteinuria, the bioactive growth factors transforming growth factor-β (TGF-β) and hepatocyte growth factor (HGF) are ultrafiltered into tubular fluid, can interact with respective receptors in apical tubular cell membranes, increase the expression and basolateral secretion of C-C-chemokines, which interact with cells in the renal interstitium and indirectly cause myofibroblasts to increase the expression of extracellular matrix proteins.
HGF and TGF-β were measured by Western blot and bioassay in glomerular ultrafiltrate that was collected by nephron micropuncture from rats with diabetic nephropathy and control rats. Proximal tubular and collecting duct cells were incubated with diluted proximal tubular fluid or recombinant human HGF (rhHGF) or rhTGF-β and expression of C-C-chemokines was measured by RT-PCR and ELISA. Interactions of tubular cell chemokines with macrophages and indirectly with myofibroblasts were also examined using cell culture models.
In rats with glomerular proteinuria due to diabetic nephropathy mature, bioactive HGF as well as active and latent TGF-β were detected in early proximal tubular fluid. Specific HGF-and TGF-β type II receptors were expressed in apical tubular membranes more in diabetic compared to control rats. Incubation of cultured mouse proximal tubular cells (mPTC) or medullary collecting duct cells (mIMCD-3) with diabetic rat proximal tubular fluid increased MCP-1 and RANTES mRNA levels as well as secreted peptide up to threefold. In contrast, high glucose (450 mg/dL), bovine serum albumin (BSA) or rat albumin (each at 100 μg/mL) or 10 nmol/L insulin-like growth factor-I (IGF-I; which was also present in glomerular ultrafiltrate in rats with diabetic nephropathy) did not affect expression of these chemokines. Recombinant human TGF-β as well as rhHGF each increased MCP-1 and RANTES mRNA as well as peptide levels several-fold. In cultured macrophages MCP-1 raised the secretion of TGF-β, which in turn increased the expression of collagen type I and III as well as fibronectin in renal interstitial myofibroblasts about 2.5 to 4-fold.
Proteinuria-induced progressive renal interstitial fibrosis may be caused by glomerular ultrafiltration of high molecular weight bioactive growth factors, HGF and TGF-β, which “activate” tubular cells through apical membranes. These apical signals are translated into basolateral events that are recognized by cells in the interstitium, such as the basolateral secretion of the C-C-chemokines MCP-1 and RANTES, which may (via macrophages) stimulate interstitial myofibroblasts, and thus lead to accumulation of extracellular matrix proteins and progressive interstitial fibrosis.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>10720953</pmid><doi>10.1046/j.1523-1755.2000.00928.x</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Associated diseases and complications Biological and medical sciences Body Fluids - metabolism Chemokine CCL2 - metabolism Chemokine CCL5 - metabolism Diabetes. Impaired glucose tolerance Diabetic Nephropathies - metabolism Diabetic Nephropathies - pathology diabetic nephropathy Disease Progression Endocrine pancreas. Apud cells (diseases) Endocrinopathies Extracellular Matrix Proteins - metabolism fibronectin Fibrosis - metabolism Glomerulonephritis hepatocyte growth factor Hepatocyte Growth Factor - metabolism Humans Kidney - cytology Kidney - metabolism Kidney Glomerulus - metabolism Kidney Tubules, Proximal - metabolism MCP-1 Medical sciences Mice Nephrology. Urinary tract diseases Nephropathies. Renovascular diseases. Renal failure proteinuria Proto-Oncogene Proteins c-met - metabolism Rats Rats, Sprague-Dawley Receptors, Transforming Growth Factor beta - metabolism TGF-β Transforming Growth Factor beta - metabolism |
| title | Role of glomerular ultrafiltration of growth factors in progressive interstitial fibrosis in diabetic nephropathy |
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