CIRBP Increases the Synthesis and Secretion of Steroid Hormones by Activating Autophagy in Yak Granule Cells

Rui Zhang, Yangyang Pan, Meng Wang, Jinglei Wang, TongXiang Zhang, Ling Zhao, Ruihua Xu, Yaying Wang, Xiaohong Han, Xiaolin Ye, Yan Cui, Sijiu Yu
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Abstract

As a regulatory protein that upregulates transcription in response to various stresses, cold-induced RNA-binding protein (CIRBP) is involved in a variety of physiological pathological processes in cells. However, little is known about the role of CIRBP in regulating autophagy and the synthesis and secretion of ovarian steroid hormones (estradiol E2 and progesterone P4). This study aimed to explore whether the synthetic secretion of ovarian steroid hormones is related to CIRBP-regulated autophagy. We detected the differential expression of CIRBP, LC3, E2 and P4 in YGCs cultured at mild low temperature (32 °C) for 6 and 12 h. CIRBP, LC3, E2 and P4 expression was increased in response to low temperature in YGCs. In order to illustrate that the changes in secretion of E2/P4 and autophagy might be caused by CIRBP induced by low temperature, we overexpressed CIRBP in YGCs cultured in vitro to detect its effects on autophagy and steroid hormone synthesis and secretion. We found that overexpression of CIRBP can induce autophagy of YGCs and enhance the synthesis and secretion of E2 and P4, suggesting that mild hypothermia may activate autophagy by inducing the expression of CIRBP and enhance the synthesis and secretion of E2 and P4. To further explore the relationship between CIRBP regulated autophagy and steroid hormone synthesis and secretion, we verified it by regulating autophagy. The results showed that Inhibition of autophagy significantly reversed CIRBP overexpression-enhanced autophagy and synthetic secretion of E2, P4 in YGCs, while activated autophagy showed similar results to overexpression of CIRBP. In conclusion, our data suggest that autophagy is involved in the synthesis and secretion of YGCs E2 and P4 and is associated with overexpression of CIRBP.

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CIRBP 通过激活雅克颗粒细胞的自噬作用增加类固醇激素的合成和分泌
冷诱导 RNA 结合蛋白(CIRBP)作为一种在各种压力下上调转录的调节蛋白,参与了细胞的多种生理病理过程。然而,人们对 CIRBP 在调节自噬和卵巢类固醇激素(雌二醇 E2 和孕酮 P4)的合成和分泌中的作用知之甚少。本研究旨在探讨卵巢类固醇激素的合成分泌是否与CIRBP调控的自噬有关。我们检测了在温和低温(32 °C)下培养 6 小时和 12 小时的 YGCs 中 CIRBP、LC3、E2 和 P4 的不同表达。为了说明低温引起的E2/P4分泌和自噬变化可能是由CIRBP引起的,我们在体外培养的YGCs中过表达了CIRBP,以检测其对自噬和类固醇激素合成与分泌的影响。我们发现,过表达CIRBP可诱导YGCs自噬,并促进E2和P4的合成和分泌,这表明轻度低温可通过诱导CIRBP的表达激活自噬,并促进E2和P4的合成和分泌。为了进一步探讨CIRBP调控自噬与类固醇激素合成和分泌的关系,我们通过调控自噬进行了验证。结果表明,抑制自噬可明显逆转 CIRBP 过表达对 YGCs 自噬和 E2、P4 合成分泌的促进作用,而激活自噬的结果与 CIRBP 过表达相似。总之,我们的数据表明,自噬参与了YGCs E2和P4的合成和分泌,并与CIRBP的过表达有关。
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