دورية أكاديمية
R168H and V165X mutant podocin might induce different degrees of podocyte injury via different molecular mechanisms
| العنوان: | R168H and V165X mutant podocin might induce different degrees of podocyte injury via different molecular mechanisms |
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| المؤلفون: | Fan, Qingfeng, Zhang, Han, Ding, Jie, Liu, Shufang, Miao, Jing, Xing, Yan, Yu, Zihua, Guan, Na |
| المساهمون: | Ding, J (reprint author), Peking Univ, Hosp 1, Dept Pediat, Beijing 100034, Peoples R China., Peking Univ, Hosp 1, Dept Pediat, Beijing 100034, Peoples R China., Peking Univ, Hosp 3, Dept Pediat, Beijing 100083, Peoples R China., Fuzhou Gen Hosp, Dept Pediat, Fuzhou 350025, Peoples R China. |
| المصدر: | SCI ; PubMed |
| بيانات النشر: | genes to cells |
| سنة النشر: | 2009 |
| المجموعة: | Peking University Institutional Repository (PKU IR) / 北京大学机构知识库 |
| مصطلحات موضوعية: | FOCAL SEGMENTAL GLOMERULOSCLEROSIS, ENDOPLASMIC-RETICULUM STRESS, GLOMERULAR SLIT DIAPHRAGM, EPITHELIAL-CELL INJURY, NEPHROTIC SYNDROME, PLASMA-MEMBRANE, NPHS2, TRPC6, CHANNEL, KIDNEY |
| الوصف: | A lot of mutations of podocin, a key protein of podocyte slit diaphragm (SD), have been found both in hereditary and sporadic focal segmental glomeruloscleorosis (FSGS). Nevertheless, the mechanisms of podocyte injury induced by mutant podocins are still unclear. A compound heterozygous podocin mutation was identified in our FSGS patient, leading to a truncated (podocin V165X) and a missense mutant protein (podocin R168H), respectively. Here, it was explored whether and how both mutant podocins induce podocyte injury in the in vitro cultured podocyte cell line. Our results showed that podocin R168H induced more significant podocyte apoptosis and expression changes in more podocyte molecules than podocin V165X. Podocyte injury caused by the normal localized podocin V165X was effectively inhibited by TRPC6 knockdown. The abnormal retention of podocin R168H in endoplasmic reticulum ( ER) resulted in the mis-localizations of other critical SD molecules nephrin, CD2AP and TRPC6, and significantly up-regulated ER stress markers Bip/grp78, p-PERK and caspase-12. These results implicated that podocin R168H and podocin V165X induced different degrees of podocyte injury, which might be resulted from different molecular mechanisms. Our findings provided some possible clues for further exploring the pharmacological targets to the proteinuria induced by different mutant podocins. ; Cell Biology ; Genetics & Heredity ; SCI(E) ; PubMed ; 3 ; ARTICLE ; 9 ; 1079-1090 ; 14 |
| نوع الوثيقة: | journal/newspaper |
| اللغة: | English |
| تدمد: | 1356-9597 |
| العلاقة: | GENES TO CELLS.2009,14,(9),1079-1090.; 669376; http://hdl.handle.net/20.500.11897/160277Test; WOS:000269540700004 |
| DOI: | 10.1111/j.1365-2443.2009.01336.x |
| الإتاحة: | https://doi.org/20.500.11897/160277Test https://doi.org/10.1111/j.1365-2443.2009.01336.xTest https://hdl.handle.net/20.500.11897/160277Test |
| رقم الانضمام: | edsbas.E15DF3F2 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 13569597 |
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| DOI: | 10.1111/j.1365-2443.2009.01336.x |