Maternal protein restriction induces renal AT2R promoter hypomethylation in salt‐sensitive, hypertensive rats
| Autor: | Masashi Fukuoka, Naoya Sugimoto, Misa Kaji, Yuki Aanzai, Hirohiko Hohjoh, Lila Otani, Huijuan Jia, Moe Miyoshi, Hisanori Kato, Yasuhisa Imakado, Tetsuo Murakami |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty lcsh:TX341-641 030204 cardiovascular system & hematology 03 medical and health sciences 0302 clinical medicine Spontaneously hypertensive rat Transcription (biology) Casein Internal medicine salt sensitivity medicine maternal protein restriction Original Research Messenger RNA Fetus Stroke‐Prone Spontaneously Hypertensive Rat DNA methylation Chemistry Promoter 030104 developmental biology Endocrinology In utero angiotensin type 2 receptor lcsh:Nutrition. Foods and food supply Food Science |
| Zdroj: | Food Science & Nutrition, Vol 9, Iss 3, Pp 1452-1459 (2021) Food Science & Nutrition |
| ISSN: | 2048-7177 |
| Popis: | Scope We previously demonstrated that protein restriction in utero induced salt‐sensitive hypertension and changed renal levels of angiotensin type 2 receptor (AT2R) in Stroke‐Prone Spontaneously Hypertensive Rat (SHRSP). Here, we investigated if this characteristic alteration of AT2R is related to AT2R DNA methylation profiles. Methods and Results First, we examined the relation between AT2R DNA methylation and its promoter activity in vitro. Luciferase assays revealed a negative correlation between these two variables. Next, we fed SHRSP dams and grand‐dams a control 20% casein diet or a 9% casein diet during pregnancy. Adult offspring and grand‐offspring were supplied either water or 1% saline solution for 2 weeks. Renal AT2R promoter DNA near the TATA‐box was hypomethylated, mRNA expression was suppressed, and protein expression tended to be higher, in adult offspring of mothers fed a low casein diet. Moreover, adult grand‐offspring exhibited high blood pressure after salt loading, along with suppressed transcription of AT2R mRNA and elevated translated protein. Conclusions Under a fetal environment of protein restriction, the increase in protein expression due to hypomethylation of the AT2R promoter region occurs as a response to increased salt sensitivity, and controlling this mechanism may be important for the prevention of hypertension. Offspring and grand‐offspring derived from rats fed low‐protein diets during pregnancy showed significantly increased blood pressure upon drinking saline solution (increasing the risk of salt‐sensitive hypertension). As a potential molecular mechanism, we found that the AT2R level that regulates blood pressure is increased through DNA hypomethylation in the promoter region. Controlling this characteristic change observed in response to salt loading could help prevention and treatment of hypertension. |
| Databáze: | OpenAIRE |
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