Roles of transforming growth factor-? and phosphatidylinositol 3-kinase isoforms in integrin ?1-mediated bio-behaviors of mouse lung telocytes.

ABSTRACT: 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 TGF?1-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 PI3Kp110?, PI3K?/?, PKC?, or GSK3, followed by TGF?1 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 TGF?1-induced PI3Kp110?, PI3K?/?, PKC?, 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.

SUBMITTER: Song D 

PROVIDER: S-EPMC6936066 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature