20-HETE and EETs in Diabetic Nephropathy: A Novel Mechanistic Pathway
<p>Diabetic nephropathy (DN), a major complication of diabetes, is characterized by hypertrophy, extracellular matrix accumulation, fibrosis and proteinuria leading to loss of renal function. Hypertrophy is a major factor inducing proximal tubular epithelial cells injury. However, the mechanis...
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| مؤلفون آخرون: | , , , , , , |
| منشور في: |
2013
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| _version_ | 1864513512734195712 |
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| author | Stephanie Eid (440990) |
| author2 | Rita Maalouf (440991) Ayad A. Jaffa (9717731) Joseph Nassif (440992) Ahmed Hamdy (440993) Awad Rashid (440994) Fuad N. Ziyadeh (11702369) Assaad A. Eid (11256112) |
| author2_role | author author author author author author author |
| author_facet | Stephanie Eid (440990) Rita Maalouf (440991) Ayad A. Jaffa (9717731) Joseph Nassif (440992) Ahmed Hamdy (440993) Awad Rashid (440994) Fuad N. Ziyadeh (11702369) Assaad A. Eid (11256112) |
| author_role | author |
| dc.creator.none.fl_str_mv | Stephanie Eid (440990) Rita Maalouf (440991) Ayad A. Jaffa (9717731) Joseph Nassif (440992) Ahmed Hamdy (440993) Awad Rashid (440994) Fuad N. Ziyadeh (11702369) Assaad A. Eid (11256112) |
| dc.date.none.fl_str_mv | 2013-08-02T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1371/journal.pone.0070029 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/20-HETE_and_EETs_in_Diabetic_Nephropathy_A_Novel_Mechanistic_Pathway/26021605 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Diabetes mellitus Epithelial cells Glucose Protein expression Kidneys Glucose metabolism Collagens Metabolic pathways |
| dc.title.none.fl_str_mv | 20-HETE and EETs in Diabetic Nephropathy: A Novel Mechanistic Pathway |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p>Diabetic nephropathy (DN), a major complication of diabetes, is characterized by hypertrophy, extracellular matrix accumulation, fibrosis and proteinuria leading to loss of renal function. Hypertrophy is a major factor inducing proximal tubular epithelial cells injury. However, the mechanisms leading to tubular injury is not well defined. In our study, we show that exposure of rats proximal tubular epithelial cells to high glucose (HG) resulted in increased extracellular matrix accumulation and hypertrophy. HG treatment increased ROS production and was associated with alteration in CYPs 4A and 2C11 expression concomitant with alteration in 20-HETE and EETs formation. HG-induced tubular injury were blocked by HET0016, an inhibitor of CYPs 4A. In contrast, inhibition of EETs promoted the effects of HG on cultured proximal tubular cells. Our results also show that alteration in CYPs 4A and 2C expression and 20HETE and EETs formation regulates the activation of the mTOR/p70S6Kinase pathway, known to play a major role in the development of DN. In conclusion, we show that hyperglycemia in diabetes has a significant effect on the expression of Arachidonic Acid (AA)-metabolizing CYPs, manifested by increased AA metabolism, and might thus alter kidney function through alteration of type and amount of AA metabolites.</p><h2>Other Information</h2> <p> Published in: PLoS ONE<br> License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1371/journal.pone.0070029" target="_blank">https://dx.doi.org/10.1371/journal.pone.0070029</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_fb5b176e9c68e7d48fea8ab556e586d9 |
| identifier_str_mv | 10.1371/journal.pone.0070029 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26021605 |
| publishDate | 2013 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | 20-HETE and EETs in Diabetic Nephropathy: A Novel Mechanistic PathwayStephanie Eid (440990)Rita Maalouf (440991)Ayad A. Jaffa (9717731)Joseph Nassif (440992)Ahmed Hamdy (440993)Awad Rashid (440994)Fuad N. Ziyadeh (11702369)Assaad A. Eid (11256112)Biomedical and clinical sciencesClinical sciencesMedical biochemistry and metabolomicsDiabetes mellitusEpithelial cellsGlucoseProtein expressionKidneysGlucose metabolismCollagensMetabolic pathways<p>Diabetic nephropathy (DN), a major complication of diabetes, is characterized by hypertrophy, extracellular matrix accumulation, fibrosis and proteinuria leading to loss of renal function. Hypertrophy is a major factor inducing proximal tubular epithelial cells injury. However, the mechanisms leading to tubular injury is not well defined. In our study, we show that exposure of rats proximal tubular epithelial cells to high glucose (HG) resulted in increased extracellular matrix accumulation and hypertrophy. HG treatment increased ROS production and was associated with alteration in CYPs 4A and 2C11 expression concomitant with alteration in 20-HETE and EETs formation. HG-induced tubular injury were blocked by HET0016, an inhibitor of CYPs 4A. In contrast, inhibition of EETs promoted the effects of HG on cultured proximal tubular cells. Our results also show that alteration in CYPs 4A and 2C expression and 20HETE and EETs formation regulates the activation of the mTOR/p70S6Kinase pathway, known to play a major role in the development of DN. In conclusion, we show that hyperglycemia in diabetes has a significant effect on the expression of Arachidonic Acid (AA)-metabolizing CYPs, manifested by increased AA metabolism, and might thus alter kidney function through alteration of type and amount of AA metabolites.</p><h2>Other Information</h2> <p> Published in: PLoS ONE<br> License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1371/journal.pone.0070029" target="_blank">https://dx.doi.org/10.1371/journal.pone.0070029</a></p>2013-08-02T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1371/journal.pone.0070029https://figshare.com/articles/journal_contribution/20-HETE_and_EETs_in_Diabetic_Nephropathy_A_Novel_Mechanistic_Pathway/26021605CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/260216052013-08-02T03:00:00Z |
| spellingShingle | 20-HETE and EETs in Diabetic Nephropathy: A Novel Mechanistic Pathway Stephanie Eid (440990) Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Diabetes mellitus Epithelial cells Glucose Protein expression Kidneys Glucose metabolism Collagens Metabolic pathways |
| status_str | publishedVersion |
| title | 20-HETE and EETs in Diabetic Nephropathy: A Novel Mechanistic Pathway |
| title_full | 20-HETE and EETs in Diabetic Nephropathy: A Novel Mechanistic Pathway |
| title_fullStr | 20-HETE and EETs in Diabetic Nephropathy: A Novel Mechanistic Pathway |
| title_full_unstemmed | 20-HETE and EETs in Diabetic Nephropathy: A Novel Mechanistic Pathway |
| title_short | 20-HETE and EETs in Diabetic Nephropathy: A Novel Mechanistic Pathway |
| title_sort | 20-HETE and EETs in Diabetic Nephropathy: A Novel Mechanistic Pathway |
| topic | Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Diabetes mellitus Epithelial cells Glucose Protein expression Kidneys Glucose metabolism Collagens Metabolic pathways |