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首页> 外文期刊>Cell metabolism >PTH/PTHrP Receptor Mediates Cachexia in Models of Kidney Failure and Cancer
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PTH/PTHrP Receptor Mediates Cachexia in Models of Kidney Failure and Cancer

机译：PTH / PTHrP受体介导肾脏衰竭和癌症模型中的恶病质

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Cachexia is a wasting syndrome associated with elevated basal energy expenditure and loss of adipose and muscle tissues. It accompanies many chronic diseases including renal failure and cancer and is an important risk factor for mortality. Our recent work demonstrated that tumor-derived PTHrP drives adipose tissue browning and cachexia. Here, we show that PTH is involved in stimulating a thermogenic gene program in 5/6 nephrectomized mice that suffer from cachexia. Fat-specific knockout of PTHR blocked adipose browning and wasting. Surprisingly, loss of PTHR in fat tissue also preserved muscle mass and improved muscle strength. Similarly, PTHR knockout mice were resistant to cachexia driven by tumors. Our results demonstrate that PTHrP and PTH mediate wasting through a common mechanism involving PTHR, and there exists an unexpected crosstalk mechanism between wasting of fat tissue and skeletal muscle. Targeting the PTH/PTHrP pathway may have therapeutic uses in humans with cachexia.
机译：恶病质是与基础能量消耗增加以及脂肪和肌肉组织损失相关的消耗综合征。它伴随着许多慢性疾病，包括肾衰竭和癌症，并且是死亡率的重要危险因素。我们最近的工作表明，肿瘤来源的PTHrP会导致脂肪组织褐变和恶病质。在这里，我们表明PTH参与刺激恶病质5/6肾切除的小鼠中的产热基因程序。 PTHR的脂肪特异性敲除可阻止脂肪褐变和浪费。出人意料的是，脂肪组织中PTHR的丢失还保留了肌肉质量并改善了肌肉强度。同样，PTHR基因敲除小鼠对肿瘤驱动的恶病质有抵抗力。我们的研究结果表明，PTHrP和PTH通过涉及PTHR的常见机制来介导消瘦，并且在脂肪组织和骨骼肌消瘦之间存在意外的串扰机制。靶向PTH / PTHrP途径可能对恶病质患者有治疗作用。

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