Increased fibroblast growth factor-21 in chronic kidney disease is a trade-off between survival benefit and blood pressure dysregulation
Autor: | Hiroshi Kurosu, Kazunori Karasawa, Makoto Kuro-o, Keisei Kosaki, Takuya Kishi, Masahide Yoshida, Kazuhiro Shiizaki, Toshihiro Nakano, Hiroaki Mizukami, Seiji Maeda, Shoya Mori, Naoki Usui, Kosaku Nitta, Tatsushi Onaka, Kunihiro Yamagata, Ruri Kaneda, Yutaka Miura, Masahiro Matsui |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Sympathetic nervous system Baroreceptor FGF21 lcsh:Medicine Blood Pressure Pressoreceptors 030204 cardiovascular system & hematology urologic and male genital diseases Article 03 medical and health sciences Mice 0302 clinical medicine Endocrinology Internal medicine medicine Endocrine system Animals Humans Renal Insufficiency Chronic lcsh:Science Mice Knockout Multidisciplinary business.industry lcsh:R medicine.disease Pathophysiology Fibroblast Growth Factors Disease Models Animal 030104 developmental biology medicine.anatomical_structure Blood pressure Nephrology lcsh:Q business Kidney disease Hormone |
Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019) |
ISSN: | 2045-2322 |
Popis: | Circulating levels of fibroblast growth factor-21 (FGF21) start increasing in patients with chronic kidney disease (CKD) since early stages during the cause of disease progression. FGF21 is a liver-derived hormone that induces responses to stress through acting on hypothalamus to activate the sympathetic nervous system and the hypothalamus-pituitary-adrenal endocrine axis. However, roles that FGF21 plays in pathophysiology of CKD remains elusive. Here we show in mice that FGF21 is required to survive CKD but responsible for blood pressure dysregulation. When introduced with CKD, Fgf21−/− mice died earlier than wild-type mice. Paradoxically, these Fgf21−/− CKD mice escaped several complications observed in wild-type mice, including augmentation of blood pressure elevating response and activation of the sympathetic nervous system during physical activity and increase in serum noradrenalin and corticosterone levels. Supplementation of FGF21 by administration of an FGF21-expressing adeno-associated virus vector recapitulated these complications in wild-type mice and restored the survival period in Fgf21−/− CKD mice. In CKD patients, high serum FGF21 levels are independently associated with decreased baroreceptor sensitivity. Thus, increased FGF21 in CKD can be viewed as a survival response at the sacrifice of blood pressure homeostasis. |
Databáze: | OpenAIRE |
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