Next Article in Journal
Challenges in Using Circulating Micro-RNAs as Biomarkers for Cardiovascular Diseases
Previous Article in Journal
Enhanced Efficacy of PEGylated Liposomal Cisplatin: In Vitro and In Vivo Evaluation
Previous Article in Special Issue
Sirtuin 3 Activation by Honokiol Decreases Unilateral Ureteral Obstruction-Induced Renal Inflammation and Fibrosis via Regulation of Mitochondrial Dynamics and the Renal NF-κB-TGF-β1/Smad Signaling Pathway
Open AccessArticle

Underlying Histopathology Determines Response to Oxidative Stress in Cultured Human Primary Proximal Tubular Epithelial Cells

by Muhammad Ali Khan 1,2,3,4,5,6, Xiangju Wang 3,4, Kurt T.K. Giuliani 2,3,4, Purba Nag 3,4, Anca Grivei 3,4, Jacobus Ungerer 2,3, Wendy Hoy 1,7, Helen Healy 1,3,4,7, Glenda Gobe 1,2,5,7,† and Andrew J. Kassianos 3,4,7,*,†
1
NHMRC CKD CRE (CKD.QLD), University of Queensland, Brisbane 4029, Queensland, Australia
2
Faculty of Medicine, University of Queensland, Brisbane 4006, Queensland, Australia
3
Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland, Brisbane 4029, Queensland, Australia
4
Kidney Health Service, Royal Brisbane and Women’s Hospital, Brisbane 4029, Queensland, Australia
5
Kidney Disease Research Collaborative, Princess Alexandra Hospital and University of Queensland, Translational Research Institute, Brisbane 4102, Queensland, Australia
6
Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Dhaka, Bangladesh
7
Centre for Chronic Disease, Faculty of Medicine, University of Queensland, Brisbane 4029, Queensland, Australia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(2), 560; https://doi.org/10.3390/ijms21020560
Received: 24 December 2019 / Revised: 9 January 2020 / Accepted: 13 January 2020 / Published: 15 January 2020
(This article belongs to the Special Issue Inflammation and Oxidative Stress in Kidney Disease)
Proximal tubular epithelial cells (PTEC) are key players in the progression of kidney diseases. PTEC studies to date have primarily used mouse models and transformed human PTEC lines. However, the translatability of these models to human kidney disease has been questioned. In this study, we investigated the phenotypic and functional response of human primary PTEC to oxidative stress, an established driver of kidney disease. Furthermore, we examined the functional contribution of the underlying histopathology of the cortical tissue used to generate our PTEC. We demonstrated that human primary PTEC from both histologically ‘normal’ and ‘diseased’ cortical tissue responded to H2O2-induced oxidative stress with significantly elevated mitochondrial superoxide levels, DNA damage, and significantly decreased proliferation. The functional response of ‘normal’ PTEC to oxidative stress mirrored the reported pathogenesis of human kidney disease, with significantly attenuated mitochondrial function and increased cell death. In contrast, ‘diseased’ PTEC were functionally resistant to oxidative stress, with maintenance of mitochondrial function and cell viability. This selective survival of ‘diseased’ PTEC under oxidizing conditions is reminiscent of the in vivo persistence of maladaptive PTEC following kidney injury. We are now exploring the impact that these differential PTEC responses have in the therapeutic targeting of oxidative stress pathways. View Full-Text
Keywords: human primary proximal tubular epithelial cells; oxidative stress; acute kidney injury; chronic kidney disease human primary proximal tubular epithelial cells; oxidative stress; acute kidney injury; chronic kidney disease
Show Figures

Figure 1

MDPI and ACS Style

Khan, M.A.; Wang, X.; Giuliani, K.T.; Nag, P.; Grivei, A.; Ungerer, J.; Hoy, W.; Healy, H.; Gobe, G.; Kassianos, A.J. Underlying Histopathology Determines Response to Oxidative Stress in Cultured Human Primary Proximal Tubular Epithelial Cells. Int. J. Mol. Sci. 2020, 21, 560.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop