Parathyroid hormone-producing cells exist in adipose tissues surrounding the parathyroid glands in hemodialysis patients with secondary hyperparathyroidism
Parathyroid hormone-producing cells exist in adipose tissues surrounding the parathyroid glands in hemodialysis patients with secondary hyperparathyroidism
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DOI：
10.1038/s41598-020-60045-y
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发表时间：
2020-02-24
影响因子：
4.6
通讯作者：
Fukagawa, Masafumi
中科院分区：
文献类型：
--
作者：
Kakuta, Takatoshi;Sawada, Kaichiro;Fukagawa, Masafumi
在继发性甲状旁腺功能亢进（SHPT）患者中，检查了增生的甲状旁腺周围脂肪组织中可能的异位甲状旁腺激素（PTH）产生。甲状旁腺切除术中切除的31例患者的脂肪组织体外培养显示23例（74.2%）患者分泌PTH。在体外甲状旁腺的脂肪组织中，22例（71.0%）患者，11例（35.5%）患者的非粘附脂肪和4例（28.6%）患者的胸腺中检测到PTH分泌。免疫组织化学显示，培养前切除的脂肪组织中，PTH和GCM 2阳性细胞集落与脂肪细胞错综复杂地交织在一起。当将SHPT患者的甲状旁腺实质移植到具有诱导SHPT的免疫缺陷裸鼠的甲状腺中时，移植物在移植后1至3个半月分泌人PTH，并表达脂肪细胞标记物，PPAR γ 2和围脂蛋白A，而移植物在移植前不表达。这些发现表明，在进行甲状旁腺切除术时，彻底清除甲状旁腺周围的脂肪组织的重要性。我们推测，这些异位PTH产生细胞是在增生实质细胞结节状生长期间与脂肪祖细胞一起从腺体沿着推出的甲状旁腺实质细胞，并且这些细胞在SHPT中增殖，形成与脂肪细胞错综复杂交织的PTH产生细胞集落。
Possible ectopic parathyroid hormone (PTH) production in adipose tissues surrounding hyperplastic parathyroid glands was examined in patients with secondary hyperparathyroidism (SHPT). In vitro culture of adipose tissues from 31 patients excised during parathyroidectomy showed PTH secretion in 23 (74.2%) patients. In vitro PTH secretion was detected in adipose tissues adhered to the parathyroid glands from 22 (71.0%) patients, in not-adhered adipose from 11 (35.5%) and in the thymus from four (28.6%) patients. Immunohistochemistry revealed colonies of PTH- and GCM2-positive cells intricately intertwined with adipocytes in excised adipose tissues prior to culture. When pieces of parathyroid parenchyma from SHPT patients were transplanted into the thyroid of immunodeficient nude rats with induced SHPT, the transplants secreted human PTH for one to three-and-half months after transplantation and expressed adipocyte markers, PPAR gamma 2 and perilipin A, that the transplants did not express prior to transplantation. These findings indicate the importance of thoroughly removing adipose tissues surrounding the parathyroid glands when performing parathyroidectomy. We speculate that these ectopic PTH-producing cells are parathyroid parenchymal cells pushed out from the glands along with adipocyte progenitors during nodular growth of hyperplastic parenchymal cells and that these cells proliferate in SHPT, forming colonies PTH-producing cells intricately intertwined with adipocytes.