title: Bone marrow-derived mesenchymal stem cells inhibit the proliferation of hepatic stellate cells by inhibiting the transforming growth factor β pathway.
abstract: Bone marrow-derived mesenchymal stem cells (BM-MSCs) are considered to be a potential therapy for end-stage liver disease. However, the therapeutic mechanism of BM-MSCs remains unclear. The aim of the current study was to investigate the role of paracrine signaling in BM‑MSCs in liver cirrhosis in vitro. Human BM‑MSCs and hepatic stellate cells (HSCs) were cultured using a vertical double cell co‑culture system. Groups were divided into HSCs alone (control group) and the co‑culture system of BM‑MSCs with HSCs (experimental group). HSC morphology was observed by inverted phase contrast microscopy. The proliferative capacity of HSCs was measured with the MTT assay and flow cytometry. Hoechst staining was performed to examine the apoptosis of HSCs. Transforming growth factor (TGF)‑β1 and Smad7 mRNA expression were detected by reverse transcription‑quantitative polymerase chain reaction and western blotting. BM‑MSCs did not inhibit the proliferation of HSCs at 24 h, however significantly inhibited the proliferation of HSCs at 48 and 72 h. BM‑MSCs additionally induced the apoptosis of HSCs at 48 h. The concentration of TGF‑β1 in the supernatant at 24 h and 48 h in the co‑cultured system was observed to be significantly lower than in the control group (P<0.05). The level of TGF‑β1 mRNA in the experimental group at 48 h was significantly lower than the control group, however Smad7 mRNA levels were significantly greater than in the control group. Additionally, TGF‑β1 protein levels were significantly lower than in the control group, however levels of Smad7 were greater than the control group. It was concluded that BM‑MSCs are able to inhibit the proliferation and promote the apoptosis of HSCs. In addition, the mechanism may be associated with inhibition of the TGF-β1/Smad pathway in HSCs.
authors.affiliation: Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Li-Ting
authors.initials: LT
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, The Central Hospital of Baoji, Baoji, Shanxi 721008, P.R. China.
authors.forename: Xue-Qin
authors.initials: XQ
authors.lastname: Fang
authors.affiliation: Department of Laboratory Medicine, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Qing-Feng
authors.initials: QF
authors.lastname: Chen
authors.affiliation: Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Institute of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xiao
authors.affiliation: Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Xue-Bin
authors.initials: XB
authors.lastname: Peng
authors.affiliation: School of Life Science, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Sheng-Xiang
authors.initials: SX
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Mao
mesh_terms: D017209:Apoptosis; D002450:Cell Communication; D002460:Cell Line; D049109:Cell Proliferation; D018920:Coculture Techniques; D015870:Gene Expression; D055166:Hepatic Stellate Cells / Q000502:physiology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D015398:Signal Transduction; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
chemical_list: C497806:SMAD7 protein, human; D051906:Smad7 Protein; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1