Hyperglycemia: GDNF-EGR1 pathway target renal epithelial cell migration and apoptosis in diabetic renal embryopathy.
Maternal hyperglycemia can inhibit morphogenesis of ureteric bud branching, Glial cell line-derived neurotrophilic factor (GDNF) is a key regulator of the initiation of ureteric branching. Early growth response gene-1 (EGR-1) is an immediate early gene. Preliminary study found EGR-1 persistently exp...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3585314?pdf=render |
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| author | Ching-Yuang Lin Tze-Yi Lin Min-Chun Lee Shih-Chieh Chen Jeng-Shou Chang |
| author_facet | Ching-Yuang Lin Tze-Yi Lin Min-Chun Lee Shih-Chieh Chen Jeng-Shou Chang |
| author_sort | Ching-Yuang Lin |
| collection | DOAJ |
| description | Maternal hyperglycemia can inhibit morphogenesis of ureteric bud branching, Glial cell line-derived neurotrophilic factor (GDNF) is a key regulator of the initiation of ureteric branching. Early growth response gene-1 (EGR-1) is an immediate early gene. Preliminary study found EGR-1 persistently expressed with GDNF in hyperglycemic environment. To evaluate the potential relationship of hyperglycemia-GDNF-EGR-1 pathway, in vitro human renal proximal tubular epithelial (HRPTE) cells as target and in vivo streptozotocin-induced mice model were used. Our in vivo microarray, real time-PCR and confocal morphological observation confirmed apoptosis in hyperglycemia-induced fetal nephropathy via activation of the GDNF/MAPK/EGR-1 pathway at E12-E15. Detachment between ureteric branch and metanephrons, coupled with decreasing number and collapse of nephrons on Day 1 newborn mice indicate hyperglycemic environment suppress ureteric bud to invade metanephric rudiment. In vitro evidence proved that high glucose suppressed HRPTE cell migration and enhanced GDNF-EGR-1 pathway, inducing HRPTE cell apoptosis. Knockdown of EGR-1 by siRNA negated hyperglycemic suppressed GDNF-induced HRPTE cells. EGR-1 siRNA also reduced GDNF/EGR-1-induced cRaf/MEK/ERK phosphorylation by 80%. Our findings reveal a novel mechanism of GDNF/MAPK/EGR-1 activation playing a critical role in HRPTE cell migration, apoptosis and fetal hyperglycemic nephropathy. |
| first_indexed | 2024-04-13T18:08:22Z |
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| id | doaj.art-77be13704c1b4a85b6e11ed7a8988247 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T18:08:22Z |
| publishDate | 2013-01-01 |
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| series | PLoS ONE |
| spelling | doaj.art-77be13704c1b4a85b6e11ed7a89882472022-12-22T02:36:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5673110.1371/journal.pone.0056731Hyperglycemia: GDNF-EGR1 pathway target renal epithelial cell migration and apoptosis in diabetic renal embryopathy.Ching-Yuang LinTze-Yi LinMin-Chun LeeShih-Chieh ChenJeng-Shou ChangMaternal hyperglycemia can inhibit morphogenesis of ureteric bud branching, Glial cell line-derived neurotrophilic factor (GDNF) is a key regulator of the initiation of ureteric branching. Early growth response gene-1 (EGR-1) is an immediate early gene. Preliminary study found EGR-1 persistently expressed with GDNF in hyperglycemic environment. To evaluate the potential relationship of hyperglycemia-GDNF-EGR-1 pathway, in vitro human renal proximal tubular epithelial (HRPTE) cells as target and in vivo streptozotocin-induced mice model were used. Our in vivo microarray, real time-PCR and confocal morphological observation confirmed apoptosis in hyperglycemia-induced fetal nephropathy via activation of the GDNF/MAPK/EGR-1 pathway at E12-E15. Detachment between ureteric branch and metanephrons, coupled with decreasing number and collapse of nephrons on Day 1 newborn mice indicate hyperglycemic environment suppress ureteric bud to invade metanephric rudiment. In vitro evidence proved that high glucose suppressed HRPTE cell migration and enhanced GDNF-EGR-1 pathway, inducing HRPTE cell apoptosis. Knockdown of EGR-1 by siRNA negated hyperglycemic suppressed GDNF-induced HRPTE cells. EGR-1 siRNA also reduced GDNF/EGR-1-induced cRaf/MEK/ERK phosphorylation by 80%. Our findings reveal a novel mechanism of GDNF/MAPK/EGR-1 activation playing a critical role in HRPTE cell migration, apoptosis and fetal hyperglycemic nephropathy.http://europepmc.org/articles/PMC3585314?pdf=render |
| spellingShingle | Ching-Yuang Lin Tze-Yi Lin Min-Chun Lee Shih-Chieh Chen Jeng-Shou Chang Hyperglycemia: GDNF-EGR1 pathway target renal epithelial cell migration and apoptosis in diabetic renal embryopathy. PLoS ONE |
| title | Hyperglycemia: GDNF-EGR1 pathway target renal epithelial cell migration and apoptosis in diabetic renal embryopathy. |
| title_full | Hyperglycemia: GDNF-EGR1 pathway target renal epithelial cell migration and apoptosis in diabetic renal embryopathy. |
| title_fullStr | Hyperglycemia: GDNF-EGR1 pathway target renal epithelial cell migration and apoptosis in diabetic renal embryopathy. |
| title_full_unstemmed | Hyperglycemia: GDNF-EGR1 pathway target renal epithelial cell migration and apoptosis in diabetic renal embryopathy. |
| title_short | Hyperglycemia: GDNF-EGR1 pathway target renal epithelial cell migration and apoptosis in diabetic renal embryopathy. |
| title_sort | hyperglycemia gdnf egr1 pathway target renal epithelial cell migration and apoptosis in diabetic renal embryopathy |
| url | http://europepmc.org/articles/PMC3585314?pdf=render |
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