Bone Morphogenetic Protein (BMP)-7 expression is decreased in human hypertensive nephrosclerosis
<p>Abstract</p> <p>Background</p> <p>Bone Morphogenetic Protein (BMP)-7 is protective in different animal models of acute and chronic kidney disease. Its role in human kidneys, and in particular hypertensive nephrosclerosis, has thus far not been described.</p> &l...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-11-01
|
| Series: | BMC Nephrology |
| Online Access: | http://www.biomedcentral.com/1471-2369/11/31 |
| _version_ | 1818808835632005120 |
|---|---|
| author | Cohen Clemens D Schmid Holger Lange Katharina Ahrens Katharina Bramlage Peter Bevanda Jelena Maatouk Imad Koziolek Michael Tampe Björn Bramlage Carsten P Kretzler Matthias Müller Gerhard A |
| author_facet | Cohen Clemens D Schmid Holger Lange Katharina Ahrens Katharina Bramlage Peter Bevanda Jelena Maatouk Imad Koziolek Michael Tampe Björn Bramlage Carsten P Kretzler Matthias Müller Gerhard A |
| author_sort | Cohen Clemens D |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Bone Morphogenetic Protein (BMP)-7 is protective in different animal models of acute and chronic kidney disease. Its role in human kidneys, and in particular hypertensive nephrosclerosis, has thus far not been described.</p> <p>Methods</p> <p>BMP-7 mRNA was quantified using real-time PCR and localised by immunostaining in tissue samples from normal and nephrosclerotic human kidneys. The impact of angiotensin (AT)-II and the AT-II receptor antagonist telmisartan on BMP-7 mRNA levels and phosphorylated Smad 1/5/8 (pSmad 1/5/8) expression was quantified in proximal tubular cells (HK-2). Functional characteristics of BMP-7 were evaluated by testing its influence on TGF-β induced epithelial-to-mesenchymal transition (EMT), expression of TGF-β receptor type I (TGF-βRI) and phosphorylated Smad 2 (pSmad 2) as well as on TNF-α induced apoptosis of proximal tubular cells.</p> <p>Results</p> <p>BMP-7 was predominantly found in the epithelia of the distal tubule and the collecting duct and was less abundant in proximal tubular cells. In sclerotic kidneys, BMP-7 was significantly decreased as demonstrated by real-time PCR and immunostaining. AT-II stimulation in HK-2 cells led to a significant decrease of BMP-7 and pSmad 1/5/8, which was partially ameliorated upon co-incubation with telmisartan. Only high concentrations of BMP-7 (100 ng/ml) were able to reverse TNF-α-induced apoptosis and TGF-β-induced EMT in human proximal tubule cells possibly due to a decreased expression of TGF-βRI. In addition, BMP-7 was able to reverse TGF-β-induced phosphorylation of Smad 2.</p> <p>Conclusions</p> <p>The findings suggest a protective role for BMP-7 by counteracting the TGF-β and TNF-α-induced negative effects. The reduced expression of BMP-7 in patients with hypertensive nephrosclerosis may imply loss of protection and regenerative potential necessary to counter the disease.</p> |
| first_indexed | 2024-12-18T19:47:52Z |
| format | Article |
| id | doaj.art-6a52f7e8dd704c8e9cff3ab5fd345828 |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-12-18T19:47:52Z |
| publishDate | 2010-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj.art-6a52f7e8dd704c8e9cff3ab5fd3458282022-12-21T20:55:17ZengBMCBMC Nephrology1471-23692010-11-011113110.1186/1471-2369-11-31Bone Morphogenetic Protein (BMP)-7 expression is decreased in human hypertensive nephrosclerosisCohen Clemens DSchmid HolgerLange KatharinaAhrens KatharinaBramlage PeterBevanda JelenaMaatouk ImadKoziolek MichaelTampe BjörnBramlage Carsten PKretzler MatthiasMüller Gerhard A<p>Abstract</p> <p>Background</p> <p>Bone Morphogenetic Protein (BMP)-7 is protective in different animal models of acute and chronic kidney disease. Its role in human kidneys, and in particular hypertensive nephrosclerosis, has thus far not been described.</p> <p>Methods</p> <p>BMP-7 mRNA was quantified using real-time PCR and localised by immunostaining in tissue samples from normal and nephrosclerotic human kidneys. The impact of angiotensin (AT)-II and the AT-II receptor antagonist telmisartan on BMP-7 mRNA levels and phosphorylated Smad 1/5/8 (pSmad 1/5/8) expression was quantified in proximal tubular cells (HK-2). Functional characteristics of BMP-7 were evaluated by testing its influence on TGF-β induced epithelial-to-mesenchymal transition (EMT), expression of TGF-β receptor type I (TGF-βRI) and phosphorylated Smad 2 (pSmad 2) as well as on TNF-α induced apoptosis of proximal tubular cells.</p> <p>Results</p> <p>BMP-7 was predominantly found in the epithelia of the distal tubule and the collecting duct and was less abundant in proximal tubular cells. In sclerotic kidneys, BMP-7 was significantly decreased as demonstrated by real-time PCR and immunostaining. AT-II stimulation in HK-2 cells led to a significant decrease of BMP-7 and pSmad 1/5/8, which was partially ameliorated upon co-incubation with telmisartan. Only high concentrations of BMP-7 (100 ng/ml) were able to reverse TNF-α-induced apoptosis and TGF-β-induced EMT in human proximal tubule cells possibly due to a decreased expression of TGF-βRI. In addition, BMP-7 was able to reverse TGF-β-induced phosphorylation of Smad 2.</p> <p>Conclusions</p> <p>The findings suggest a protective role for BMP-7 by counteracting the TGF-β and TNF-α-induced negative effects. The reduced expression of BMP-7 in patients with hypertensive nephrosclerosis may imply loss of protection and regenerative potential necessary to counter the disease.</p>http://www.biomedcentral.com/1471-2369/11/31 |
| spellingShingle | Cohen Clemens D Schmid Holger Lange Katharina Ahrens Katharina Bramlage Peter Bevanda Jelena Maatouk Imad Koziolek Michael Tampe Björn Bramlage Carsten P Kretzler Matthias Müller Gerhard A Bone Morphogenetic Protein (BMP)-7 expression is decreased in human hypertensive nephrosclerosis BMC Nephrology |
| title | Bone Morphogenetic Protein (BMP)-7 expression is decreased in human hypertensive nephrosclerosis |
| title_full | Bone Morphogenetic Protein (BMP)-7 expression is decreased in human hypertensive nephrosclerosis |
| title_fullStr | Bone Morphogenetic Protein (BMP)-7 expression is decreased in human hypertensive nephrosclerosis |
| title_full_unstemmed | Bone Morphogenetic Protein (BMP)-7 expression is decreased in human hypertensive nephrosclerosis |
| title_short | Bone Morphogenetic Protein (BMP)-7 expression is decreased in human hypertensive nephrosclerosis |
| title_sort | bone morphogenetic protein bmp 7 expression is decreased in human hypertensive nephrosclerosis |
| url | http://www.biomedcentral.com/1471-2369/11/31 |
| work_keys_str_mv | AT cohenclemensd bonemorphogeneticproteinbmp7expressionisdecreasedinhumanhypertensivenephrosclerosis AT schmidholger bonemorphogeneticproteinbmp7expressionisdecreasedinhumanhypertensivenephrosclerosis AT langekatharina bonemorphogeneticproteinbmp7expressionisdecreasedinhumanhypertensivenephrosclerosis AT ahrenskatharina bonemorphogeneticproteinbmp7expressionisdecreasedinhumanhypertensivenephrosclerosis AT bramlagepeter bonemorphogeneticproteinbmp7expressionisdecreasedinhumanhypertensivenephrosclerosis AT bevandajelena bonemorphogeneticproteinbmp7expressionisdecreasedinhumanhypertensivenephrosclerosis AT maatoukimad bonemorphogeneticproteinbmp7expressionisdecreasedinhumanhypertensivenephrosclerosis AT koziolekmichael bonemorphogeneticproteinbmp7expressionisdecreasedinhumanhypertensivenephrosclerosis AT tampebjorn bonemorphogeneticproteinbmp7expressionisdecreasedinhumanhypertensivenephrosclerosis AT bramlagecarstenp bonemorphogeneticproteinbmp7expressionisdecreasedinhumanhypertensivenephrosclerosis AT kretzlermatthias bonemorphogeneticproteinbmp7expressionisdecreasedinhumanhypertensivenephrosclerosis AT mullergerharda bonemorphogeneticproteinbmp7expressionisdecreasedinhumanhypertensivenephrosclerosis |