Tian Xinning, Yao Wantao, Tan Jin, Hu Zhangle, Liu Jingwen
Department of Cardiology, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
School of Basic Medicine, Anhui Medical University, Hefei, 230032, China.
Sci Rep. 2025 Mar 7;15(1):8052. doi: 10.1038/s41598-025-92571-y.
The kidney is a vital organ responsible for removing toxins, producing urine, and regulating homeostasis. Developmental defects in the kidney lead to various congenital abnormalities that impair renal function. Gdf11, a member of the transforming growth factor β family, is associated with numerous renal abnormalities. In the early developmental stage, the pronephric duct and hindgut open into the cloaca, and Gdf11 shows significant expression in the hindgut of mice. However, the molecular and cellular roles of gdf11 in kidney and cloaca organogenesis remain unclear. Our study revealed that pronephros and cloaca formation were significantly disrupted upon gdf11 deletion or knockdown in zebrafish. Additionally, we found that the TGF-β pathway acts downstream of Gdf11 in promoting pronephros and cloaca development. Treatment with a TGF-β small molecule activator partially rescued the pronephros and cloaca developmental defects observed in gdf11 mutants. In summary, our findings provide strong evidence of a critical link between pronephros/cloaca formation and TGF-β signaling mediated by Gdf11. Our study also provides new insight into diseases related to renal and cloaca development.
肾脏是一个重要器官，负责清除毒素、产生尿液和调节体内平衡。肾脏发育缺陷会导致各种先天性异常，损害肾功能。生长分化因子11（Gdf11）是转化生长因子β家族的成员之一，与多种肾脏异常有关。在发育早期阶段，前肾管和后肠通入泄殖腔，并且Gdf11在小鼠后肠中呈现显著表达。然而，Gdf11在肾脏和泄殖腔器官发生中的分子和细胞作用仍不清楚。我们的研究表明，在斑马鱼中Gdf11缺失或敲低后，前肾和泄殖腔的形成会受到显著破坏。此外，我们发现TGF-β信号通路在促进前肾和泄殖腔发育过程中作用于Gdf11的下游。用TGF-β小分子激活剂进行处理可部分挽救在Gdf11突变体中观察到的前肾和泄殖腔发育缺陷。总之，我们的研究结果为前肾/泄殖腔形成与由Gdf11介导的TGF-β信号传导之间的关键联系提供了有力证据。我们的研究还为与肾脏和泄殖腔发育相关的疾病提供了新的见解。
