| 刘星辰,王 璟,刘博阳,张 娇,刘王佳,苗登顺.PTH缺失通过诱导肾脏细胞衰老和衰老相关分泌表型分子表达而加速肾脏纤维化[J].,2024,(16):3006-3012 |
| PTH缺失通过诱导肾脏细胞衰老和衰老相关分泌表型分子表达而加速肾脏纤维化 |
| Lack of PTH Accelerates Renal Fibrosis through Induction of Cellular Senescence and Upregulation of Senescence-associated Secretory Phenotype Molecules |
| 投稿时间：2023-08-21 修订日期：2023-09-18 |
| DOI：10.13241/j.cnki.pmb.2024.16.002 |
| 中文关键词: 旁甲状旁腺素 肾纤维化 细胞老化 衰老相关分泌表型 |
| 英文关键词: Parathyroid hormone Renal fibrosis Cellular senescence Senescence-associated secretory phenotype |
| 基金项目:国家自然科学基金面上项目（82172504） |
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| 中文摘要: |
| 摘要 目的：探究旁甲状旁腺素（Parathyroid hormone, PTH）缺失对肾脏纤维化及其相关机制的影响。方法：采用2月龄野生型（WT）小鼠和PTH基因缺失（PTH-/-）小鼠为模型，通过组织病理学染色、免疫组化、Western blot和qRT-PCR等方法，检测并比较两组小鼠肾脏组织中胶原蛋白沉积、细胞增殖、衰老和衰老相关分泌表型（Senescence-associated secretory phenotype, SASP）分子表达的差异。结果：与WT组相比，PTH-/-小鼠肾脏组织中胶原蛋白沉积和I型胶原mRNA表达显著增加。PTH缺失还导致肾脏组织抗氧化酶SOD1表达下降，DNA双链断裂标志分子γ-H2A.X表达和活性氧水平升高。同时，PTH-/-小鼠肾脏组织中细胞增殖标志物Ki67和PCNA表达下调，而细胞周期抑制蛋白p16、p53和衰老相关β-半乳糖苷酶活性升高。除此之外，SASP分子IL-6、MMP3和MMP13在PTH-/-小鼠肾脏中出现明显高表达。结论：PTH缺失能够加速肾脏纤维化进程，其机制可能与诱导肾脏细胞氧化应激、DNA损伤增加，细胞增殖受阻、衰老加剧，以及SASP分子表达上调有关。该研究揭示了PTH在维持肾脏稳态中的重要作用。 |
| 英文摘要: |
| ABSTRACT Objective: This study aimed to investigate the effects of parathyroid hormone (Parathyroid hormone, PTH) deficiency on renal fibrosis and its underlying mechanisms. Methods: Two-month-old wild-type (WT) mice and PTH gene-deficient (PTH-/-) mice were used as models. Tissue histological staining, immunohistochemistry, Western blot, and qRT-PCR were performed to compare the differences in collagen deposition, cell proliferation, cellular senescence, and senescence-associated secretory phenotype (Senescence-associated secretory phenotype, SASP) molecule expression in the renal tissue between the two groups of mice. Results: Compared with the WT group, PTH-/- mice showed significantly increased collagen deposition and expression of type I collagen mRNA in renal tissue. PTH deficiency also led to decreased expression of the antioxidant enzyme SOD1 in renal tissue, increased expression of the DNA double-strand break marker γ-H2A.X, and elevated levels of reactive oxygen species. Moreover, PTH-/- mice exhibited downregulation of the cell proliferation markers Ki67 and PCNA, increased expression of cell cycle arrest proteins p16 and p53, and elevated senescence-associated β-galactosidase activity. In addition, SASP molecules IL-6, MMP3, and MMP13 were significantly upregulated in the renal tissue of PTH-/- mice. Conclusion: PTH deficiency can accelerate the process of renal fibrosis, likely through induction of oxidative stress and DNA damage in renal cells, inhibition of cell proliferation, exacerbation of cellular senescence, and upregulation of SASP molecule expression. This study sheds light on the important role of PTH in maintaining renal homeostasis. |
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