Nrf2 phosphorylation contributes to acquisition of pericyte reprogramming via the PKCδ pathway

Pericytes (PCs) are vascular mural cells embedded in the basement membrane of micro blood vessels. It has been proposed using a C.B-17 mouse model of stroke that normal brain PCs are converted to ischemic PCs (iPCs), some of which express various stem cell markers. We previously reported that nuclea...

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Main Authors: Rika Sakuma, Yusuke Minato, Seishi Maeda, Hideshi Yagi
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Neurobiology of Disease
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Online Access:http://www.sciencedirect.com/science/article/pii/S0969996125000403
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author Rika Sakuma
Yusuke Minato
Seishi Maeda
Hideshi Yagi
author_facet Rika Sakuma
Yusuke Minato
Seishi Maeda
Hideshi Yagi
author_sort Rika Sakuma
collection DOAJ
description Pericytes (PCs) are vascular mural cells embedded in the basement membrane of micro blood vessels. It has been proposed using a C.B-17 mouse model of stroke that normal brain PCs are converted to ischemic PCs (iPCs), some of which express various stem cell markers. We previously reported that nuclear factor erythroid-2-related factor 2 (Nrf2) protected against oxidative stress following ischemia and promoted the PC reprogramming process. The present study examined the molecular mechanisms underlying the induction of Nrf2. We revealed that oxidative stress and pNrf2 induced by stroke proceeded the expression of nestin in meningeal cells and reactive PCs within the post-stroke area. PKCδ inhibitor treatment suppressed pNrf2 activation and restored the down-regulated expression of stem cell markers in iPCs in vitro. The PKCδ inhibitor treatment also suppressed the production of iPCs. These results suggest the potential of Nrf2 phosphorylation via PKCδ as a novel strategy for the treatment of ischemic injury.
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institution Kabale University
issn 1095-953X
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publishDate 2025-03-01
publisher Elsevier
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series Neurobiology of Disease
spelling doaj-art-73b581aa15f549b7ad9b2b112e8105c72025-02-08T04:59:33ZengElsevierNeurobiology of Disease1095-953X2025-03-01206106824Nrf2 phosphorylation contributes to acquisition of pericyte reprogramming via the PKCδ pathwayRika Sakuma0Yusuke Minato1Seishi Maeda2Hideshi Yagi3Corresponding author.; Department of Anatomy and Cell Biology, Faculty of Medicine, Hyogo Medical University, 1-1, Mukogawa-cho, Nishinomiya-shi, Hyogo 663-8501, JapanDepartment of Anatomy and Cell Biology, Faculty of Medicine, Hyogo Medical University, 1-1, Mukogawa-cho, Nishinomiya-shi, Hyogo 663-8501, JapanDepartment of Anatomy and Cell Biology, Faculty of Medicine, Hyogo Medical University, 1-1, Mukogawa-cho, Nishinomiya-shi, Hyogo 663-8501, JapanDepartment of Anatomy and Cell Biology, Faculty of Medicine, Hyogo Medical University, 1-1, Mukogawa-cho, Nishinomiya-shi, Hyogo 663-8501, JapanPericytes (PCs) are vascular mural cells embedded in the basement membrane of micro blood vessels. It has been proposed using a C.B-17 mouse model of stroke that normal brain PCs are converted to ischemic PCs (iPCs), some of which express various stem cell markers. We previously reported that nuclear factor erythroid-2-related factor 2 (Nrf2) protected against oxidative stress following ischemia and promoted the PC reprogramming process. The present study examined the molecular mechanisms underlying the induction of Nrf2. We revealed that oxidative stress and pNrf2 induced by stroke proceeded the expression of nestin in meningeal cells and reactive PCs within the post-stroke area. PKCδ inhibitor treatment suppressed pNrf2 activation and restored the down-regulated expression of stem cell markers in iPCs in vitro. The PKCδ inhibitor treatment also suppressed the production of iPCs. These results suggest the potential of Nrf2 phosphorylation via PKCδ as a novel strategy for the treatment of ischemic injury.http://www.sciencedirect.com/science/article/pii/S0969996125000403PericytesStrokeNeural stem cellspNrf2PKCδ pathway
spellingShingle Rika Sakuma
Yusuke Minato
Seishi Maeda
Hideshi Yagi
Nrf2 phosphorylation contributes to acquisition of pericyte reprogramming via the PKCδ pathway
Neurobiology of Disease
Pericytes
Stroke
Neural stem cells
pNrf2
PKCδ pathway
title Nrf2 phosphorylation contributes to acquisition of pericyte reprogramming via the PKCδ pathway
title_full Nrf2 phosphorylation contributes to acquisition of pericyte reprogramming via the PKCδ pathway
title_fullStr Nrf2 phosphorylation contributes to acquisition of pericyte reprogramming via the PKCδ pathway
title_full_unstemmed Nrf2 phosphorylation contributes to acquisition of pericyte reprogramming via the PKCδ pathway
title_short Nrf2 phosphorylation contributes to acquisition of pericyte reprogramming via the PKCδ pathway
title_sort nrf2 phosphorylation contributes to acquisition of pericyte reprogramming via the pkcδ pathway
topic Pericytes
Stroke
Neural stem cells
pNrf2
PKCδ pathway
url http://www.sciencedirect.com/science/article/pii/S0969996125000403
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AT seishimaeda nrf2phosphorylationcontributestoacquisitionofpericytereprogrammingviathepkcdpathway
AT hideshiyagi nrf2phosphorylationcontributestoacquisitionofpericytereprogrammingviathepkcdpathway