title: miR-375 regulates rat alveolar epithelial cell trans-differentiation by inhibiting Wnt/β-catenin pathway.
abstract: Alveolar epithelial cell (AEC) trans-differentiation is a process where type II alveolar epithelial cells (AEC II) trans-differentiate into type I alveolar epithelial cells (AEC I) during lung recovery after various injuries, in which AEC I are damaged. This process is critical for lung tissue repair. MicroRNAs are a group of small RNAs that regulate gene expression at the post-transcriptional level. They have the potential to regulate almost every aspect of cell physiology. However, whether AEC trans-differentiation is regulated by microRNAs is completely unknown. In this study, we found that miR-375 was downregulated during AEC trans-differentiation. The overexpression of miR-375 with an adenoviral vector inhibited alveolar epithelial trans-differentiation as indicated by an increase in the AEC II marker, surfactant protein C, and decreases in the AEC I markers, T1α and advanced glycosylation end product-specific receptor. miR-375 also inhibited the Wnt/β-catenin pathway. The constitutively activation of Wnt/β-catenin signaling with a stabilized form of β-catenin blocked the miR-375 effects. Frizzled 8 was identified as a target of miR-375. In summary, our results demonstrate that miR-375 regulates AEC trans-differentiation through the Wnt/β-catenin pathway. This discovery may provide new targets for therapeutic intervention to benefit lung recovery from injuries.
authors: Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA.
authors: Yang
authors: Y
authors: Wang
authors: Chaoqun
authors: C
authors: Huang
authors: Narendranath
authors: N
authors: Reddy Chintagari
authors: Manoj
authors: M
authors: Bhaskaran
authors: Tingting
authors: T
authors: Weng
authors: Yujie
authors: Y
authors: Guo
authors: Xiao
authors: X
authors: Xiao
authors: Lin
authors: L
authors: Liu
mesh_terms: D000818:Animals; D054338:Cell Transdifferentiation / Q000235:genetics*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000196:embryology / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000235:genetics; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000037:antagonists & inhibitors
chemical_list: C504124:FZD8 protein, rat; C574979:MIRN375 microRNA, rat; D035683:MicroRNAs; D011956:Receptors, Cell Surface; D051176:beta Catenin
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