Stromal Cell-Derived Factor 1 Protects Brain Vascular Endothelial Cells from Radiation-Induced Brain Damage
Stromal cell-derived factor 1 (SDF-1) and its main receptor, CXC chemokine receptor 4 (CXCR4), play a critical role in endothelial cell function regulation during cardiogenesis, angiogenesis, and reendothelialization after injury. The expression of CXCR4 and SDF-1 in brain endothelial cells decrease...
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MDPI AG
2019-10-01
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| Online Access: | https://www.mdpi.com/2073-4409/8/10/1230 |
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| author | Jong-Ik Heo Kwang Il Kim Sang-Keun Woo Joong Sun Kim Kyu Jin Choi Hae-June Lee Kwang Seok Kim |
| author_facet | Jong-Ik Heo Kwang Il Kim Sang-Keun Woo Joong Sun Kim Kyu Jin Choi Hae-June Lee Kwang Seok Kim |
| author_sort | Jong-Ik Heo |
| collection | DOAJ |
| description | Stromal cell-derived factor 1 (SDF-1) and its main receptor, CXC chemokine receptor 4 (CXCR4), play a critical role in endothelial cell function regulation during cardiogenesis, angiogenesis, and reendothelialization after injury. The expression of CXCR4 and SDF-1 in brain endothelial cells decreases due to ionizing radiation treatment and aging. SDF-1 protein treatment in the senescent and radiation-damaged cells reduced several senescence phenotypes, such as decreased cell proliferation, upregulated p53 and p21 expression, and increased senescence-associated beta-galactosidase (SA-β-gal) activity, through CXCR4-dependent signaling. By inhibiting extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription protein 3 (STAT3), we confirmed that activation of both is important in recovery by SDF-1-related mechanisms. A CXCR4 agonist, ATI2341, protected brain endothelial cells from radiation-induced damage. In irradiation-damaged tissue, ATI2341 treatment inhibited cell death in the villi of the small intestine and decreased SA-β-gal activity in arterial tissue. An ischemic injury experiment revealed no decrease in blood flow by irradiation in ATI2341-administrated mice. ATI2341 treatment specifically affected CXCR4 action in mouse brain vessels and partially restored normal cognitive ability in irradiated mice. These results demonstrate that SDF-1 and ATI2341 may offer potential therapeutic approaches to recover tissues damaged during chemotherapy or radiotherapy, particularly by protecting vascular endothelial cells. |
| first_indexed | 2024-03-12T19:16:19Z |
| format | Article |
| id | doaj.art-aa651a4afe3a4569a7e6c0b7d14807c4 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T19:16:19Z |
| publishDate | 2019-10-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-aa651a4afe3a4569a7e6c0b7d14807c42023-08-02T05:32:04ZengMDPI AGCells2073-44092019-10-01810123010.3390/cells8101230cells8101230Stromal Cell-Derived Factor 1 Protects Brain Vascular Endothelial Cells from Radiation-Induced Brain DamageJong-Ik Heo0Kwang Il Kim1Sang-Keun Woo2Joong Sun Kim3Kyu Jin Choi4Hae-June Lee5Kwang Seok Kim6Divisions of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, KoreaDivisions of Radio-Isotope Applied Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, KoreaDivisions of Radio-Isotope Applied Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, KoreaK-herb Research Center, Korea Institute of Oriental Medicine, Daejeon 34054, KoreaDivisions of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, KoreaDivisions of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, KoreaDivisions of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, KoreaStromal cell-derived factor 1 (SDF-1) and its main receptor, CXC chemokine receptor 4 (CXCR4), play a critical role in endothelial cell function regulation during cardiogenesis, angiogenesis, and reendothelialization after injury. The expression of CXCR4 and SDF-1 in brain endothelial cells decreases due to ionizing radiation treatment and aging. SDF-1 protein treatment in the senescent and radiation-damaged cells reduced several senescence phenotypes, such as decreased cell proliferation, upregulated p53 and p21 expression, and increased senescence-associated beta-galactosidase (SA-β-gal) activity, through CXCR4-dependent signaling. By inhibiting extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription protein 3 (STAT3), we confirmed that activation of both is important in recovery by SDF-1-related mechanisms. A CXCR4 agonist, ATI2341, protected brain endothelial cells from radiation-induced damage. In irradiation-damaged tissue, ATI2341 treatment inhibited cell death in the villi of the small intestine and decreased SA-β-gal activity in arterial tissue. An ischemic injury experiment revealed no decrease in blood flow by irradiation in ATI2341-administrated mice. ATI2341 treatment specifically affected CXCR4 action in mouse brain vessels and partially restored normal cognitive ability in irradiated mice. These results demonstrate that SDF-1 and ATI2341 may offer potential therapeutic approaches to recover tissues damaged during chemotherapy or radiotherapy, particularly by protecting vascular endothelial cells.https://www.mdpi.com/2073-4409/8/10/1230sdf-1cxcr4ionizing radiationendothelial dysfunctionsenescencebrain disorder |
| spellingShingle | Jong-Ik Heo Kwang Il Kim Sang-Keun Woo Joong Sun Kim Kyu Jin Choi Hae-June Lee Kwang Seok Kim Stromal Cell-Derived Factor 1 Protects Brain Vascular Endothelial Cells from Radiation-Induced Brain Damage Cells sdf-1 cxcr4 ionizing radiation endothelial dysfunction senescence brain disorder |
| title | Stromal Cell-Derived Factor 1 Protects Brain Vascular Endothelial Cells from Radiation-Induced Brain Damage |
| title_full | Stromal Cell-Derived Factor 1 Protects Brain Vascular Endothelial Cells from Radiation-Induced Brain Damage |
| title_fullStr | Stromal Cell-Derived Factor 1 Protects Brain Vascular Endothelial Cells from Radiation-Induced Brain Damage |
| title_full_unstemmed | Stromal Cell-Derived Factor 1 Protects Brain Vascular Endothelial Cells from Radiation-Induced Brain Damage |
| title_short | Stromal Cell-Derived Factor 1 Protects Brain Vascular Endothelial Cells from Radiation-Induced Brain Damage |
| title_sort | stromal cell derived factor 1 protects brain vascular endothelial cells from radiation induced brain damage |
| topic | sdf-1 cxcr4 ionizing radiation endothelial dysfunction senescence brain disorder |
| url | https://www.mdpi.com/2073-4409/8/10/1230 |
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