School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou, 310023, Zhejiang, China.
Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
BMC Vet Res. 2024 May 10;20(1):186. doi: 10.1186/s12917-024-04067-y.
The current understanding to the mechanism of rumen development is limited. We hypothesized that the Hippo signaling pathway controlled the proliferation of rumen epithelium (RE) during postnatal development. In the present study, we firstly tested the changes of the Hippo signaling pathway in the RE during an early growing period from d5 to d25, and then we expanded the time range to the whole preweaning period (d10-38) and one week post weaning (d45). An in vitro experiment was also carried out to verify the function of Hippo signaling pathway during RE cell proliferation.
In the RE of lambs from d5 to d25, the expression of baculoviral IAP repeat containing (BIRC3/5) was increased, while the expressions of large tumor suppressor kinase 2 (LATS2), TEA domain transcription factor 3 (TEAD3), axin 1 (AXIN1), and MYC proto-oncogene (MYC) were decreased with rumen growth. From d10 to d38, the RE expressions of BIRC3/5 were increased, while the expressions of LATS2 and MYC were decreased, which were similar with the changes in RE from d5 to d25. From d38 to d45, different changes were observed, with the expressions of LATS1/2, MOB kinase activator 1B (MOB1B), and TEAD1 increased, while the expressions of MST1 and BIRC5 decreased. Correlation analysis showed that during the preweaning period, the RE expressions of BIRC3/5 were positively correlated with rumen development variables, while LAST2 was negatively correlated with rumen development variables. The in vitro experiment validated the changes of LATS2 and BIRC3/5 in the proliferating RE cells, which supported their roles in RE proliferation during preweaning period.
Our results suggest that the LATS2-YAP1-BIRC3/5 axis participates in the RE cell proliferation and promotes rumen growth during the preweaning period.
目前对于瘤胃发育机制的认识有限。我们假设 Hippo 信号通路在出生后发育过程中控制瘤胃上皮（RE）的增殖。在本研究中，我们首先检测了在早期生长阶段（d5 至 d25）RE 中 Hippo 信号通路的变化，然后将时间范围扩展到整个断奶前阶段（d10-38）和断奶后一周（d45）。还进行了一项体外实验来验证 Hippo 信号通路在 RE 细胞增殖过程中的功能。
在 d5 至 d25 的羔羊 RE 中，杆状病毒 IAP 重复包含物（BIRC3/5）的表达增加，而大肿瘤抑制激酶 2（LATS2）、TEA 结构域转录因子 3（TEAD3）、轴蛋白 1（AXIN1）和 MYC 原癌基因（MYC）的表达减少，伴随着瘤胃的生长。从 d10 到 d38，RE 中 BIRC3/5 的表达增加，而 LATS2 和 MYC 的表达减少，这与 d5 至 d25 的 RE 变化相似。从 d38 到 d45，观察到不同的变化，LATS1/2、MOB 激酶激活物 1B（MOB1B）和 TEAD1 的表达增加，而 MST1 和 BIRC5 的表达减少。相关性分析表明，在断奶前阶段，RE 中 BIRC3/5 的表达与瘤胃发育变量呈正相关，而 LAST2 与瘤胃发育变量呈负相关。体外实验验证了增殖 RE 细胞中 LATS2 和 BIRC3/5 的变化，支持它们在断奶前时期在 RE 增殖中的作用。
我们的结果表明，LATS2-YAP1-BIRC3/5 轴参与 RE 细胞增殖，并在断奶前期间促进瘤胃生长。
