Kallikrein Transduced Mesenchymal Stem Cells Protect against Anti-GBM Disease and Lupus Nephritis by Ameliorating Inflammation and Oxidative Stress

Yajuan Li, Indu Raman, Yong Du, Mei Yan, Soyoun Min, Jichen Yang, Xiangdong Fang, Wei Li, Jianxin Lu, Xin J. Zhou, Chandra Mohan, Quan Zhen Li

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Previously we have shown that kallikreins (klks) play a renoprotective role in nephrotoxic serum induced nephritis. In this study, we have used mesenchymal stem cells (MSCs) as vehicles to deliver klks into the injured kidneys and have measured their therapeutic effect on experimental antibody induced nephritis and lupus nephritis. Human KLK-1 (hKLK1) gene was transduced into murine MSCs using a retroviral vector to generate a stable cell line, hKLK1-MSC, expressing high levels of hKLK1. 129/svj mice subjected to anti-GBM induced nephritis were transplanted with 106 hKLK1-MSCs and hKLK1 expression was confirmed in the kidneys. Compared with vector-MSCs injected mice, the hKLK1-MSCs treated mice showed significantly reduced proteinuria, blood urea nitrogen (BUN) and ameliorated renal pathology. Using the same strategy, we treated lupus-prone B6.Sle1.Sle3 bicongenic mice with hKLK1-MSCs and demonstrated that hKLK1-MSCs delivery also attenuated lupus nephritis. Mechanistically, hKLK1-MSCs reduced macrophage and T-lymphocyte infiltration into the kidney by suppressing the expression of inflammation cytokines. Moreover, hKLK1 transduced MSCs were more resistant to oxidative stress-induced apoptosis. These findings advance genetically modified MSCs as potential gene delivery tools for targeting therapeutic agents to the kidneys in order to modulate inflammation and oxidative stress in lupus nephritis.

Original languageEnglish (US)
Article numbere67790
JournalPLoS One
Volume8
Issue number7
DOIs
StatePublished - Jul 23 2013

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Anti-Glomerular Basement Membrane Disease
kallikreins
nephritis
Lupus Nephritis
Kallikreins
Oxidative stress
Stem cells
Mesenchymal Stromal Cells
stem cells
Oxidative Stress
oxidative stress
inflammation
Inflammation
kidneys
Nephritis
Kidney
mice
antiglomerular basement membrane antibody
Genes
129 Strain Mouse

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Kallikrein Transduced Mesenchymal Stem Cells Protect against Anti-GBM Disease and Lupus Nephritis by Ameliorating Inflammation and Oxidative Stress. / Li, Yajuan; Raman, Indu; Du, Yong; Yan, Mei; Min, Soyoun; Yang, Jichen; Fang, Xiangdong; Li, Wei; Lu, Jianxin; Zhou, Xin J.; Mohan, Chandra; Li, Quan Zhen.

In: PLoS One, Vol. 8, No. 7, e67790, 23.07.2013.

Research output: Contribution to journalArticle

Li, Yajuan ; Raman, Indu ; Du, Yong ; Yan, Mei ; Min, Soyoun ; Yang, Jichen ; Fang, Xiangdong ; Li, Wei ; Lu, Jianxin ; Zhou, Xin J. ; Mohan, Chandra ; Li, Quan Zhen. / Kallikrein Transduced Mesenchymal Stem Cells Protect against Anti-GBM Disease and Lupus Nephritis by Ameliorating Inflammation and Oxidative Stress. In: PLoS One. 2013 ; Vol. 8, No. 7.
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abstract = "Previously we have shown that kallikreins (klks) play a renoprotective role in nephrotoxic serum induced nephritis. In this study, we have used mesenchymal stem cells (MSCs) as vehicles to deliver klks into the injured kidneys and have measured their therapeutic effect on experimental antibody induced nephritis and lupus nephritis. Human KLK-1 (hKLK1) gene was transduced into murine MSCs using a retroviral vector to generate a stable cell line, hKLK1-MSC, expressing high levels of hKLK1. 129/svj mice subjected to anti-GBM induced nephritis were transplanted with 106 hKLK1-MSCs and hKLK1 expression was confirmed in the kidneys. Compared with vector-MSCs injected mice, the hKLK1-MSCs treated mice showed significantly reduced proteinuria, blood urea nitrogen (BUN) and ameliorated renal pathology. Using the same strategy, we treated lupus-prone B6.Sle1.Sle3 bicongenic mice with hKLK1-MSCs and demonstrated that hKLK1-MSCs delivery also attenuated lupus nephritis. Mechanistically, hKLK1-MSCs reduced macrophage and T-lymphocyte infiltration into the kidney by suppressing the expression of inflammation cytokines. Moreover, hKLK1 transduced MSCs were more resistant to oxidative stress-induced apoptosis. These findings advance genetically modified MSCs as potential gene delivery tools for targeting therapeutic agents to the kidneys in order to modulate inflammation and oxidative stress in lupus nephritis.",
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AU - Yang, Jichen

AU - Fang, Xiangdong

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