Abstract
BackgroundTelocytes (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.MethodsGene 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.ResultsWe 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.ConclusionTCs have strong capacity of proliferation through the compensatory signaling mechanisms and contribute to the development of drug resistance due to alterations of TC sensitivity.
Highlights
Telocytes (TCs) play an important role in cell–cell communication with adjacent cells within the tissue via direct patterns or indirect ways, such as cellular junctions, production of multi-factors and extracellular vesicles [1, 2].TCs maintain local tissue homeostasis and cooperate with stem cells for organ repair and regeneration in diseases, inflammation, and fibrosis [3, 4]
The present study aims at investigating the molecular mechanisms by which the TGFβ1- integrin beta1 (ITGB1)-phosphoinositide 3-kinase (PI3K) signal pathways regulate TCs cycle and proliferation
To understand potential regulations between those factors in TCs, we firstly investigated effects of external TGFβ1 at different concentrations and time points on TCs with ITGB1 (TCITGB1+) and selected the concentration of TGFβ1 at 5 ng/ml for 48 h as the condition of further studies (Fig. 3a)
Summary
Telocytes (TCs) play an important role in cell–cell communication with adjacent cells within the tissue via direct patterns or indirect ways, such as cellular junctions, production of multi-factors and extracellular vesicles [1, 2].TCs maintain local tissue homeostasis and cooperate with stem cells for organ repair and regeneration in diseases, inflammation, and fibrosis [3, 4]. Telocytes (TCs) play an important role in cell–cell communication with adjacent cells within the tissue via direct patterns or indirect ways, such as cellular junctions, production of multi-factors and extracellular vesicles [1, 2]. Mechanisms by which bio-behaviors of TCs are regulated are still unclear. Our recent study demonstrated that the transforming growth factor beta-1 (TGFβ1) interacted with phosphoinositide 3-kinase (PI3K) and regulated the proliferation and cell cycle phases of TCs [5]. 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
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