論文 - 詳細
| RRC ID | 78033 |
|---|---|
| 著者 | Xu W, Li G, Chen Y, Ye X, Song W. |
| タイトル | A novel antidiuretic hormone governs tumour-induced renal dysfunction. |
| ジャーナル | Nature |
| Abstract |
Maintenance of renal function and fluid transport are essential for vertebrates and invertebrates to adapt to physiological and pathological challenges. Human patients with malignant tumours frequently develop detrimental renal dysfunction and oliguria, and previous studies suggest the involvement of chemotherapeutic toxicity and tumour-associated inflammation1,2. However, how tumours might directly modulate renal functions remains largely unclear. Here, using conserved tumour models in Drosophila melanogaster3, we characterized isoform F of ion transport peptide (ITPF) as a fly antidiuretic hormone that is secreted by a subset of yki3SA gut tumour cells, impairs renal function and causes severe abdomen bloating and fluid accumulation. Mechanistically, tumour-derived ITPF targets the G-protein-coupled receptor TkR99D in stellate cells of Malpighian tubules-an excretory organ that is equivalent to renal tubules4-to activate nitric oxide synthase-cGMP signalling and inhibit fluid excretion. We further uncovered antidiuretic functions of mammalian neurokinin 3 receptor (NK3R), the homologue of fly TkR99D, as pharmaceutical blockade of NK3R efficiently alleviates renal tubular dysfunction in mice bearing different malignant tumours. Together, our results demonstrate a novel antidiuretic pathway mediating tumour-renal crosstalk across species and offer therapeutic opportunities for the treatment of cancer-associated renal dysfunction. |
| 巻・号 | 624(7991) |
| ページ | 425-432 |
| 公開日 | 2023-12-1 |
| DOI | 10.1038/s41586-023-06833-8 |
| PII | 10.1038/s41586-023-06833-8 |
| PMID | 38057665 |
| MeSH | Animals Antidiuretic Agents* / metabolism Arginine Vasopressin / metabolism Cyclic GMP / metabolism Disease Models, Animal Drosophila Proteins / metabolism Drosophila melanogaster / cytology Drosophila melanogaster / metabolism Humans Kidney Diseases* / complications Kidney Diseases* / drug therapy Kidney Diseases* / metabolism Malpighian Tubules / cytology Malpighian Tubules / metabolism Mice Neoplasms* / complications Neoplasms* / metabolism Neuropeptides* / metabolism Nitric Oxide Synthase / metabolism Receptors, Neurokinin-3* / antagonists & inhibitors Receptors, Neurokinin-3* / metabolism Xenograft Model Antitumor Assays |
| IF | 42.779 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 97 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ショウジョウバエ | |