BACKGROUND Telocytes (TCs) have the capacity of cell-cell communication with adjacent cells within the tissue, contributing to tissue repair and recovery from injury. The present study aims at investigating the molecular mechanisms by which the TGFβ1-ITGB1-PI3K signal pathways regulate TC cycle and proliferation. METHODS Gene expression of integrin (ITG) family were measured in mouse primary TCs to compare with other cells. TC proliferation, movement, cell cycle, and PI3K isoform protein genes were assayed in ITGB1-negative or positive mouse lung TCs treated with the inhibition of PI3Kp110α, PI3Kα/δ, PKCβ, or GSK3, followed by TGFβ1 treatment. RESULTS We found the characters and interactions of ITG or PKC family member networks in primary mouse lung TCs, different from other cells in the lung tissue. The deletion of ITGB1 changed TCs sensitivity to treatment with multifunctional cytokines or signal pathway inhibitors. The compensatory mechanisms occur among TGFβ1-induced PI3Kp110α, PI3Kα/δ, PKCβ, or GSK3 when ITGB1 gene was deleted, leading to alterations of TC cell cycle and proliferation. Of those PI3K isoform protein genes, mRNA expression of PIK3CG altered with ITGB1-negative TC cycle and proliferation. CONCLUSION TCs have strong capacity of proliferation through the compensatory signaling mechanisms and contribute to the development of drug resistance due to alterations of TC sensitivity.

中文翻译：

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转化生长因子-β和磷脂酰肌醇3激酶同工型在整合素β1介导的小鼠肺细胞的生物学行为中的作用。

背景技术卵母细胞（TC）具有与组织中的相邻细胞进行细胞-细胞通讯的能力，有助于组织修复和从损伤中恢复。本研究旨在研究TGFβ1-ITGB1-PI3K信号通路调节TC周期和增殖的分子机制。方法测定小鼠原代TC中整合素（ITG）家族的基因表达，以与其他细胞进行比较。在用PI3Kp110α，PI3Kα/δ，PKCβ或GSK3抑制的ITGB1阴性或阳性小鼠肺TC中分析TC增殖，运动，细胞周期和PI3K亚型蛋白基因，然后进行TGFβ1处理。结果我们发现原发性小鼠肺部TCs中ITG或PKC家族成员网络的特征和相互作用与肺组织中的其他细胞不同。ITGB1的缺失改变了TCs对多功能细胞因子或信号通路抑制剂治疗的敏感性。当ITGB1基因缺失时，TGFβ1诱导的PI3Kp110α，PI3Kα/δ，PKCβ或GSK3之间发生补偿机制，从而导致TC细胞周期和增殖的改变。在那些PI3K同工型蛋白基因中，PIK3CG的mRNA表达随ITGB1阴性TC周期和增殖而改变。结论TCs通过补偿性信号传导机制具有很强的增殖能力，并且由于TC敏感性的改变而促进了耐药性的发展。在那些PI3K同工型蛋白基因中，PIK3CG的mRNA表达随ITGB1阴性TC周期和增殖而改变。结论TCs通过补偿性信号传导机制具有很强的增殖能力，并且由于TC敏感性的改变而促进了耐药性的发展。在那些PI3K同工型蛋白基因中，PIK3CG的mRNA表达随ITGB1阴性TC周期和增殖而改变。结论TCs通过补偿性信号传导机制具有很强的增殖能力，并且由于TC敏感性的改变而促进了耐药性的发展。