Bradykinin, as a Reprogramming Factor, Induces Transdifferentiation of Brain Astrocytes into Neuron-like Cells
| Autor: | Su-Jane Wang, Hsi-Lung Hsieh, Tsong-Hai Lee, Pei-Shan Liu, Velayuthaprabhu Shanmugam, Ming-Ming Tsai |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway QH301-705.5 transdifferentiation Medicine (miscellaneous) brain astrocytes Cell morphology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine matrix metalloproteinase-9 medicine Biology (General) Glial fibrillary acidic protein biology Chemistry Transdifferentiation Cell biology 030104 developmental biology medicine.anatomical_structure nervous system Cell Transdifferentiation biology.protein Neuron Stem cell bradykinin 030217 neurology & neurosurgery Astrocyte reprogramming factor |
| Zdroj: | Biomedicines Biomedicines, Vol 9, Iss 923, p 923 (2021) Volume 9 Issue 8 |
| ISSN: | 2227-9059 |
| Popis: | Kinins are endogenous, biologically active peptides released into the plasma and tissues via the kallikrein-kinin system in several pathophysiological events. Among kinins, bradykinin (BK) is widely distributed in the periphery and brain. Several studies on the neuro-modulatory actions of BK by the B2BK receptor (B2BKR) indicate that this neuropeptide also functions during neural fate determination. Previously, BK has been shown to induce differentiation of nerve-related stem cells into neuron cells, but the response in mature brain astrocytes is unknown. Herein, we used rat brain astrocyte (RBA) to investigate the effect of BK on cell transdifferentiation into a neuron-like cell morphology. Moreover, the signaling mechanisms were explored by zymographic, RT-PCR, Western blot, and immunofluorescence staining analyses. We first observed that BK induced RBA transdifferentiation into neuron-like cells. Subsequently, we demonstrated that BK-induced RBA transdifferentiation is mediated through B2BKR, PKC-δ, ERK1/2, and MMP-9. Finally, we found that BK downregulated the astrocytic marker glial fibrillary acidic protein (GFAP) and upregulated the neuronal marker neuron-specific enolase (NSE) via the B2BKR/PKC-δ/ERK pathway in the event. Therefore, BK may be a reprogramming factor promoting brain astrocytic transdifferentiation into a neuron-like cell, including downregulation of GFAP and upregulation of NSE and MMP-9 via the B2BKR/PKC-δ/ERK cascade. Here, we also confirmed the transdifferentiative event by observing the upregulated neuronal nuclear protein (NeuN). However, the electrophysiological properties of the cells after BK treatment should be investigated in the future to confirm their phenotype. |
| Databáze: | OpenAIRE |
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