{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T09:32:58Z","timestamp":1793439178963,"version":"4.5.0"},"reference-count":61,"publisher":"Radiation Research Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2021,7,30]]},"abstract":"<jats:p>The mechanism(s) of vascular regression in adult organs remains an unexplored gap. Irradiation to the kidney results in vascular regression and renal failure. The goal of this work was to determine molecular mechanism(s) of radiation-induced vascular regression and its mitigation by the drug lisinopril. Female WAG\/RijCmcr rats received either 13 Gy X-ray irradiation, sparing one leg, or no irradiation, the latter serving as age-matched controls. Some irradiated animals received lisinopril. Kidney miRNA-seq was performed 35 days postirradiation, before symptoms of nephropathy. MicroRNA expression profiles were compared with data from humans. MicroRNA targets were predicted using TargetScan and confirmed by qRT-PCR and Western blot. Renal vascular endothelial cell density was evaluated at 100 days to confirm vascular regression. The normal rat kidney microRNA profile resembled that of humans. MiR-34a was increased &gt;7-fold and emerged as the predominant rat microRNA altered by radiation. Expression of Jagged1, a ligand in the Notch pathway of vascular development and a target of miR-34a-5p was decreased by radiation but not in irradiated rats receiving lisinopril. Radiation decreased endothelial cells in the kidneys at 100 days, confirming vascular regression. In conclusion, the results of this study showed that radiation greatly increased miRNA34-a in rat kidneys, while lisinopril mitigated radiation-induced decrease of the Notch ligand, Jagged1, a molecular target of miRNA34-a.<\/jats:p>","DOI":"10.1667\/rade-20-00078.1","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T02:47:54Z","timestamp":1638154074000},"page":"611-622","source":"Crossref","is-referenced-by-count":7,"title":["Molecular Changes in miRNA in Irradiated Rat Kidneys: Role of miR-34a and its Vascular Targets in the Notch Pathway"],"prefix":"10.1667","volume":"196","author":[{"given":"Feng","family":"Gao","sequence":"first","affiliation":[{"name":"Departments of Radiation Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Dong","sequence":"additional","affiliation":[{"name":"Departments of Radiation Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Departments of Physiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayashree","family":"Narayanan","sequence":"additional","affiliation":[{"name":"Departments of Radiation Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Fish","sequence":"additional","affiliation":[{"name":"Departments of Radiation Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth R.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Departments of Radiation Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meetha","family":"Medhora","sequence":"additional","affiliation":[{"name":"Departments of Radiation Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"29","doi-asserted-by":"crossref","unstructured":"P Landgraf, M Rusu, R Sheridan, et al.  \"Cell.\"  129, \"A mammalian microRNA expression atlas based on small RNA library sequencing.\" (2007)","DOI":"10.1016\/j.cell.2007.04.040"},{"key":"3","doi-asserted-by":"crossref","unstructured":"JP Williams, SL Brown, GE Georges, et al.  \"Radiat Res.\"  173, \"Animal models for medical countermeasures to radiation exposure.\" (2010)","DOI":"10.1667\/RR1880.1"},{"key":"7","doi-asserted-by":"crossref","unstructured":"MJ Aryankalayil, S Chopra, A Makinde, et al.  \"Biomarkers.\"  23, \"Microarray analysis of miRNA expression profiles following whole body irradiation in a mouse model.\" 689 (2018)","DOI":"10.1080\/1354750X.2018.1479771"},{"key":"1","doi-asserted-by":"crossref","unstructured":"EP Cohen  and ME Robbins  \"Semin Nephrol.\"  23, \"Radiation nephropathy.\" (2003)","DOI":"10.1016\/S0270-9295(03)00093-7"},{"key":"2","doi-asserted-by":"crossref","unstructured":"LA Dawson, BD Kavanagh, AC Paulino, et al.  \"Int J Radiat Oncol Biol Phys.\"  76, \"Radiation-associated kidney injury.\" (2010)","DOI":"10.1016\/j.ijrobp.2009.02.089"},{"key":"4","doi-asserted-by":"crossref","unstructured":"BL Fish, F Gao, J Narayanan, et al.  \"Health Phys.\"  111, \"Combined hydration and antibiotics with lisinopril to mitigate acute and delayed high-dose radiation injuries to multiple organs.\" (2016)","DOI":"10.1097\/HP.0000000000000554"},{"key":"5","doi-asserted-by":"crossref","unstructured":"EP Cohen, KG Hankey, AM Farese, et al.  \"Health Phys.\"  116, \"Radiation nephropathy in a nonhuman primate model of partial-body irradiation with minimal bone marrow sparing\u2013Part 1: Acute and chronic kidney injury and the influence of neupogen.\" (2019)","DOI":"10.1097\/HP.0000000000000960"},{"key":"6","doi-asserted-by":"crossref","unstructured":"A Sukalo, D Deljo, A Krupalija, et al.  \"Med Arch.\"  70, \"Treatment of hypertension with combination of lisinopril\/hydrochlorothiazide.\" 299 (2016)","DOI":"10.5455\/medarh.2016.70.299-302"},{"key":"8","doi-asserted-by":"crossref","unstructured":"S Bhayana, F Song, J Jacob, et al.  \"Radiat Res.\"  188, \"Urinary miRNAs as biomarkers for noninvasive evaluation of radiation-induced renal tubular injury.\" (2017)","DOI":"10.1667\/RR14828.1"},{"key":"9","doi-asserted-by":"crossref","unstructured":"SN Ghosh, Q Wu, M Mader, et al.  \"Int J Radiat Oncol Biol Phys.\"  74, \"Vascular injury after whole thoracic x-ray irradiation in the rat.\" (2009)","DOI":"10.1016\/j.ijrobp.2009.01.006"},{"key":"10","doi-asserted-by":"crossref","unstructured":"JE Baker, BL Fish, J Su, et al.  \"Int J Radiat Biol.\"  85, \"10 Gy total body irradiation increases risk of coronary sclerosis, degeneration of heart structure and function in a rat model.\" (2009)","DOI":"10.3109\/09553000903264473"},{"key":"11","doi-asserted-by":"crossref","unstructured":"T. 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implications for modulating arteriogenesis and angiogenesis.\" 14 (2003)","DOI":"10.1128\/MCB.23.1.14-25.2003"},{"key":"57","doi-asserted-by":"crossref","unstructured":"X Yuan, H Wu, H Xu, et al.  \"Cancer Lett.\"  369, \"Notch signaling: an emerging therapeutic target for cancer treatment.\" (2015)","DOI":"10.1016\/j.canlet.2015.07.048"},{"key":"58","doi-asserted-by":"crossref","unstructured":"D Gallahan  and R Callahan  \"Oncogene.\"  14, \"The mouse mammary tumor associated gene INT3 is a unique member of the NOTCH gene family (NOTCH4).\" (1997)","DOI":"10.1038\/sj.onc.1201035"},{"key":"59","doi-asserted-by":"crossref","unstructured":"G Zhu, Y Lin, H Liu, et al.  \"Biochem Biophys Res Commun.\"  507, \"Dll4-Notch1 signaling but not VEGF-A is essential for hyperoxia induced vessel regression in retina.\" (2018)","DOI":"10.1016\/j.bbrc.2018.11.051"},{"key":"60","doi-asserted-by":"crossref","unstructured":"FA Stewart, S Hoving, NS Russell,  \"Radiat Res.\"  174, \"Vascular damage as an underlying mechanism of cardiac and cerebral toxicity in irradiated cancer patients.\" (2010)","DOI":"10.1667\/RR1862.1"},{"key":"61","doi-asserted-by":"crossref","unstructured":"M Boerma  and M Hauer-Jensen  \"Cardiol Res Pract.\"  2011, \"Preclinical research into basic mechanisms of radiation-induced heart disease.\" (2010)","DOI":"10.4061\/2011\/858262"}],"container-title":["Radiation Research"],"original-title":[],"deposited":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T08:50:08Z","timestamp":1793436608000},"score":1,"resource":{"primary":{"URL":"https:\/\/bioone.org\/journals\/radiation-research\/volume-196\/issue-6\/RADE-20-00078.1\/Molecular-Changes-in-miRNA-in-Irradiated-Rat-Kidneys--Role\/10.1667\/RADE-20-00078.1.full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,30]]},"references-count":61,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,12,1]]}},"URL":"https:\/\/doi.org\/10.1667\/rade-20-00078.1","relation":{},"ISSN":["0033-7587","1938-5404"],"issn-type":[{"value":"0033-7587","type":"print"},{"value":"1938-5404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,30]]}}}