Congratulations to professor Lucia M. Moreira and professor Bao-Liang Song for publishing their paper on Nature

In November 2020, professor Lucia M. Moreira from British Heart Foundation Centre of Research Excellence published a paper titled Paracrine signalling by cardiac calcitonin controls atrial fibrogenesis and arrhythmia on Nature. And professor Bao-Liang Song from College of Life Sciences, Wuhan University published a paper titled Feeding induces cholesterol biosynthesis via the mTORC1-USP20-HMGCR axis on Nature.

Atrial fbrillation, the most common cardiac arrhythmia, is an important contributor to mortality and morbidity, and particularly to the risk of stroke in humans . Atrial-tissue fbrosis is a central pathophysiological feature of atrial fbrillation that also hampers its treatment; the underlying molecular mechanisms are poorly understood and warrant investigation given the inadequacy of present therapies. Here we show that calcitonin, a hormone product of the thyroid gland involved in bone metabolism, is also produced by atrial cardiomyocytes in substantial quantities and acts as a paracrine signal that afects neighbouring collagen-producing fbroblasts to control their proliferation and secretion of extracellular matrix proteins. Global disruption of calcitonin receptor signalling in mice causes atrial fbrosis and increases susceptibility to atrial fbrillation. In mice in which liver kinase B1 is knocked down specifcally in the atria, atrial-specifc knockdown of calcitonin promotes atrial fbrosis and increases and prolongs spontaneous episodes of atrial fbrillation, whereas atrial-specifc overexpression of calcitonin prevents both atrial fbrosis and fbrillation. Human patients with persistent atrial fbrillation show sixfold lower levels of myocardial calcitonin compared to control individuals with normal heart rhythm, with loss of calcitonin receptors in the fbroblast membrane. Although transcriptome analysis of human atrial fbroblasts reveals little change after exposure to calcitonin, proteomic analysis shows extensive alterations in extracellular matrix proteins and pathways related to fbrogenesis, infection and immune responses, and transcriptional regulation. Strategies to restore disrupted myocardial calcitonin signalling thus may ofer therapeutic avenues for patients with atrial fbrillation.

The ELISA kit (CT, CEA472Hu) of Cloud-Clone brand was chosed to determine the concentation of CT in this article, we are so proud for supporting the reaserchers.

Cholesterol is an essential lipid and its synthesis is nutritionally and energetically costly1,2 . In mammals, cholesterol biosynthesis increases after feeding and is inhibited under fasting conditions3 . However, the regulatory mechanisms of cholesterol biosynthesis at the fasting–feeding transition remain poorly understood. Here we show that the deubiquitylase ubiquitin-specifc peptidase 20 (USP20) stabilizes HMG-CoA reductase (HMGCR), the rate-limiting enzyme in the cholesterol biosynthetic pathway, in the feeding state. The post-prandial increase in insulin and glucose concentration stimulates mTORC1 to phosphorylate USP20 at S132 and S134; USP20 is recruited to the HMGCR complex and antagonizes its degradation. The feeding-induced stabilization of HMGCR is abolished in mice with liver-specifc Usp20 deletion and in USP20(S132A/S134A) knock-in mice. Genetic deletion or pharmacological inhibition of USP20 markedly decreases diet-induced body weight gain, reduces lipid levels in the serum and liver, improves insulin sensitivity and increases energy expenditure. These metabolic changes are reversed by expression of the constitutively stable HMGCR(K248R). This study reveals an unexpected regulatory axis from mTORC1 to HMGCR via USP20 phosphorylation and suggests that inhibitors of USP20 could be used to lower cholesterol levels to treat metabolic diseases including hyperlipidaemia, liver steatosis, obesity and diabetes.