TY - JOUR AB - Transdifferentiation of lung fibroblasts to myofibroblasts is a crucial pathophysiological process in pulmonary fibrosis. MicroRNA‑375 (miR‑375) was initially identified as a tumor‑suppressive factor, and its expression was negatively associated with the severity of lung cancer; however, its role and potential mechanism in myofibroblast transdifferentiation and pulmonary fibrosis remain unclear. In the present study, human lung fibroblasts were stimulated with transforming growth factor‑β (TGF‑β) to induce myofibroblast transdifferentiation. A mimic and inhibitor of miR‑375, and their negative controls, were used to overexpress or suppress miR‑375 in lung fibroblasts, respectively. The mRNA expression levels of fibrotic markers, and protein expression of α‑smooth muscle actin and periostin, were subsequently detected by reverse transcription‑quantitative PCR and western blotting, to assess myofibroblast transdifferentiation. miR‑375 was markedly upregulated in human lung fibroblasts after TGF‑β stimulation. The miR‑375 mimic alleviated, whereas the miR‑375 inhibitor aggravated TGF‑β‑dependent transdifferentiation of lung fibroblasts. Mechanistically, miR‑375 prevented myofibroblast transdifferentiation and collagen synthesis by blocking the P38 mitogen‑activated protein kinases (P38) pathway, and P38 suppression abrogated the deleterious effect of the miR‑375 inhibitor on myofibroblast transdifferentiation. Furthermore, the present study revealed that mitogen‑activated protein kinase kinase 6 was involved in P38 inactivation by miR‑375. In conclusion, miR‑375 was implicated in modulating TGF‑β‑dependent transdifferentiation of lung fibroblasts, and targeting miR‑375 expression may help to develop therapeutic approaches for treating pulmonary fibrosis. AD - Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China AU - Zhang,Xinghua AU - Chen,Qian AU - Song,Hengya AU - Jiang,Wanli AU - Xie,Songping AU - Huang,Jie AU - Kang,Ganjun DA - 2020/09/01 DO - 10.3892/mmr.2020.11261 EP - 1810 IS - 3 JO - Mol Med Rep KW - microRNA‑375 myofibroblast transdifferentiation mitogen‑activated protein kinase kinase 6 P38 mitogen‑activated protein kinases PY - 2020 SN - 1791-2997 1791-3004 SP - 1803 ST - MicroRNA‑375 prevents TGF‑β‑dependent transdifferentiation of lung fibroblasts via the MAP2K6/P38 pathway T2 - Molecular Medicine Reports TI - MicroRNA‑375 prevents TGF‑β‑dependent transdifferentiation of lung fibroblasts via the MAP2K6/P38 pathway UR - https://doi.org/10.3892/mmr.2020.11261 VL - 22 ER -