title: Therapeutic Potential of Umbilical Cord Mesenchymal Stem Cells for Inhibiting Myofibroblastic Differentiation of Irradiated Human Lung Fibroblasts.
abstract: Radiation-induced lung injury (RILI) limits the benefits of radiotherapy in patients with lung cancer. Radiation-induced differentiation of lung fibroblasts to myofibroblasts plays a key role in RILI. Recent studies have shown that mesenchymal stem cells (MSCs) can protect against lung fibrosis and that Wnt/β-catenin signaling is involved in fibrotic processes. In the present study, we explored the therapeutic potential of human umbilical cord MSCs (HUMSCs) for preventing radiation-induced differentiation of human lung fibroblasts (HLFs) to myofibroblasts. There are two advantages in the use of HUMSCs; namely, they are easily obtained and have low immunogenicity. Irradiated HLFs were co-cultured with HUMSCs. Expression of α-smooth muscle actin (α-SMA), a myofibroblast marker, was measured by Western blot analysis and immunohistochemistry. Irradiation (X-rays, 5 Gy) induced the differentiation of HLFs into myofibroblasts, which was inhibited by co-culture with HUMSCs. Irradiation also caused activation of the canonical Wnt/β-catenin signaling in HLFs, as judged by increased phosphorylation of glycogen synthase kinase 3β, nuclear accumulation of β-catenin, and elevated levels of Wnt-inducible signaling protein-1 (WISP-1) in the conditioned medium. However, co-culture with HUMSCs attenuated the radiation-induced activation of the Wnt/β-catenin signaling. We also measured the expression of FRAT1 that can enhance the Wnt/β-catenin signaling by stabilizing β-catenin. Co-culture with HUMSCs decreased FRAT1 protein levels in irradiated nHLFs. Thus, co-culture with HUMSCs attenuated the radiation-induced activation of Wnt/β-catenin signaling in HLFs, thereby inhibiting myofibroblastic differentiation of HLFs. Wnt/β-catenin signaling is a potential therapeutic target for limiting RILI in patients receiving radiotherapy for lung cancer.
authors.affiliation: Respiratory Department, Navy General Hospital.
authors.forename: Chunyang
authors.initials: C
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lianru
authors.initials: L
authors.lastname: Gao
authors.forename: Ningkun
authors.initials: N
authors.lastname: Zhang
authors.forename: Huasong
authors.initials: H
authors.lastname: Feng
mesh_terms: D000704:Analysis of Variance; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000502:physiology* / Q000528:radiation effects; D005455:Fluorescent Antibody Technique; D006801:Humans; D016130:Immunophenotyping; D008168:Lung / Q000166:cytology* / Q000528:radiation effects; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D011832:Radiation Injuries / Q000503:physiopathology / Q000628:therapy*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue