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A vital role for myosin-9 in puromycin aminonucleoside-induced podocyte injury by affecting actin cytoskeleton.
Free Radic Res. 2016 Jun; 50(6):627-37.FR

Abstract

Podocyte injury is an early pathological change of many kidney diseases. In particular, the actin cytoskeleton plays an important role in maintaining the normal function of podocytes. Disruption of the actin cytoskeleton is a feature of podocyte injury in proteinuric nephropathies. Recent studies showed that myosin-9 was localized in the podocyte foot processes and was necessary in maintaining podocyte structural homeostasis. However, it is unclear whether myosin-9 maintains podocyte structure by affecting actin cytoskleton. Here, the role of myosin-9 in puromycin aminonucleoside (PAN)-induced podocyte injury was explored both in vitro and in vivo. In cultured mouse podocytes (MPC5), it was determined that PAN downregulated myosin-9 expression, disrupted the actin cytoskeleton and reduced the adhesion ability. Reduced myosin-9 expression by siRNA precipitated podocyte cytoskeletal damage and accelerated PAN-induced podocyte detachment. Overexpression of myosin-9 protected against PAN-induced podocyte detachment. Furthermore, administration of an antioxidant Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP) inhibited PAN-induced podocyte cytoskeletal damage and podocyte detachment by restoring the expression of myosin-9. In the rat PAN nephropathy model, MnTBAP could also attenuate PAN-induced reduction of myosin-9 and podocyte loss. Taken together, these findings pinpointed that oxidative stress contributed to PAN-induced podocyte injury through the repression of a cytoskeletal protein myosin-9, which provided novel insights into a potential target for the treatment of podocyte injury-associated glomerulopathies.

Authors+Show Affiliations

a Department of Nephrology , The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital , Nanjing , China ;a Department of Nephrology , The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital , Nanjing , China ;b Department of Endocrinology , Jiangsu Province Hospital of Chinese Medicine , Nanjing , China ;a Department of Nephrology , The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital , Nanjing , China ;a Department of Nephrology , The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital , Nanjing , China ;c Department of Nephrology , Nanjing Children's Hospital, Nanjing Medical University , Nanjing , China ;c Department of Nephrology , Nanjing Children's Hospital, Nanjing Medical University , Nanjing , China ;a Department of Nephrology , The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital , Nanjing , China ;a Department of Nephrology , The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital , Nanjing , China ;c Department of Nephrology , Nanjing Children's Hospital, Nanjing Medical University , Nanjing , China ; d Institute of Pediatrics , Nanjing Medical University , Nanjing , China.a Department of Nephrology , The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital , Nanjing , China ;

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

26902808

Citation

Yuan, Yanggang, et al. "A Vital Role for Myosin-9 in Puromycin Aminonucleoside-induced Podocyte Injury By Affecting Actin Cytoskeleton." Free Radical Research, vol. 50, no. 6, 2016, pp. 627-37.
Yuan Y, Zhao C, An X, et al. A vital role for myosin-9 in puromycin aminonucleoside-induced podocyte injury by affecting actin cytoskeleton. Free Radic Res. 2016;50(6):627-37.
Yuan, Y., Zhao, C., An, X., Wu, L., Wang, H., Zhao, M., Bai, M., Duan, S., Zhang, B., Zhang, A., & Xing, C. (2016). A vital role for myosin-9 in puromycin aminonucleoside-induced podocyte injury by affecting actin cytoskeleton. Free Radical Research, 50(6), 627-37. https://doi.org/10.3109/10715762.2016.1155706
Yuan Y, et al. A Vital Role for Myosin-9 in Puromycin Aminonucleoside-induced Podocyte Injury By Affecting Actin Cytoskeleton. Free Radic Res. 2016;50(6):627-37. PubMed PMID: 26902808.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A vital role for myosin-9 in puromycin aminonucleoside-induced podocyte injury by affecting actin cytoskeleton. AU - Yuan,Yanggang, AU - Zhao,Chuanyan, AU - An,Xiaofei, AU - Wu,Lin, AU - Wang,Hui, AU - Zhao,Min, AU - Bai,Mi, AU - Duan,Suyan, AU - Zhang,Bo, AU - Zhang,Aihua, AU - Xing,Changying, Y1 - 2016/03/31/ PY - 2016/2/24/entrez PY - 2016/2/24/pubmed PY - 2017/3/31/medline KW - Myosin-9 KW - oxidative stress KW - podocyte injury KW - puromycin aminonucleoside SP - 627 EP - 37 JF - Free radical research JO - Free Radic. Res. VL - 50 IS - 6 N2 - Podocyte injury is an early pathological change of many kidney diseases. In particular, the actin cytoskeleton plays an important role in maintaining the normal function of podocytes. Disruption of the actin cytoskeleton is a feature of podocyte injury in proteinuric nephropathies. Recent studies showed that myosin-9 was localized in the podocyte foot processes and was necessary in maintaining podocyte structural homeostasis. However, it is unclear whether myosin-9 maintains podocyte structure by affecting actin cytoskleton. Here, the role of myosin-9 in puromycin aminonucleoside (PAN)-induced podocyte injury was explored both in vitro and in vivo. In cultured mouse podocytes (MPC5), it was determined that PAN downregulated myosin-9 expression, disrupted the actin cytoskeleton and reduced the adhesion ability. Reduced myosin-9 expression by siRNA precipitated podocyte cytoskeletal damage and accelerated PAN-induced podocyte detachment. Overexpression of myosin-9 protected against PAN-induced podocyte detachment. Furthermore, administration of an antioxidant Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP) inhibited PAN-induced podocyte cytoskeletal damage and podocyte detachment by restoring the expression of myosin-9. In the rat PAN nephropathy model, MnTBAP could also attenuate PAN-induced reduction of myosin-9 and podocyte loss. Taken together, these findings pinpointed that oxidative stress contributed to PAN-induced podocyte injury through the repression of a cytoskeletal protein myosin-9, which provided novel insights into a potential target for the treatment of podocyte injury-associated glomerulopathies. SN - 1029-2470 UR - https://www.unboundmedicine.com/medline/citation/26902808/A_vital_role_for_myosin_9_in_puromycin_aminonucleoside_induced_podocyte_injury_by_affecting_actin_cytoskeleton_ L2 - http://www.tandfonline.com/doi/full/10.3109/10715762.2016.1155706 DB - PRIME DP - Unbound Medicine ER -