Changes in the osmolality of body fluids pose a serious danger to cells and living organisms, which have developed cellular systems to sense and respond to osmotic stress and to maintain homoeostasis of body fluid. However, these processes are incompletely understood in mammals. Here we show that apoptosis signal-regulating kinase 3 (ASK3) is predominantly expressed in the kidney and alters its kinase activity bidirectionally in response to osmotic stress. We further demonstrate that ASK3 interacts with WNK1, mutation in which causes an inherited form of hypertension in humans. Knockdown of Ask3 by short interfering RNA enhances the activation of the WNK1-SPAK/OSR1 signalling pathway. Moreover, Ask3 knockout mice exhibit a hypertensive phenotype, in addition to hyperactivation of SPAK/OSR1 in renal tubules. Our results suggest that ASK3 is a unique bidirectional responder to osmotic stress and that it has a role in the control of blood pressure as an upstream suppressor of the WNK1-SPAK/OSR1 signalling pathway.
Background and Aim
The prevalence of ulcerative colitis (UC) has been increasing in Japan. Trace elements, such as iron, zinc, magnesium, and copper, can cause digestive symptoms where there is a deficiency or excess. We focused on the dietary intake of trace elements and their associations with UC development.
Methods
A multicenter, hospital‐based case–control study was conducted in Japan. Cases were 127 newly diagnosed UC patients, and 171 age‐matched and sex‐matched hospital controls were recruited. We considered that UC patients had potentially changed their dietary habits due to disease symptoms. The dietary habits were investigated using a self‐administered diet history questionnaire to analyze the dietary intakes and frequencies at two points, the previous 1 month and 1 year before.
Results
In the assessment of dietary habits 1 year before, the highest intake of iron showed an increased odds ratio (OR) for UC on multivariate analysis (OR = 4.05, 95% confidence interval, 1.46–11.2, P < 0.01). The highest intake of zinc 1 year before showed a decreased OR for UC (OR = 0.39, 95% confidence interval, 0.18–0.85, P = 0.01). Intakes of magnesium and copper had no significant association with UC. Because most UC cases had experienced the first symptom of UC within the previous 11 months, these intakes at 1 year before represented an association with pre‐illness dietary habits.
Conclusion
A high intake of iron has some effect on the development of UC. In contrast, a high intake of zinc has a protective effect on the development of UC.
A third of Japanese women suffer from dysmenorrhea that requires analgesics, and the prevalence of dysmenorrhea generally shows inverse relationships with parity and age.
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