title: The Orphan Receptor Tyrosine Kinase ROR2 Facilitates MSCs to Repair Lung Injury in ARDS Animal Model.
abstract: There are some limitations to the therapeutic effects of mesenchymal stem cells (MSCs) on acute respiratory distress syndrome (ARDS) due to their low engraftment and differentiation rates in lungs. We found previously that noncanonical Wnt5a signaling promoted the differentiation of mouse MSCs (mMSCs) into type II alveolar epithelial cells (AT II cells), conferred resistance to oxidative stress, and promoted migration of MSCs in vitro. As receptor tyrosine kinase-like orphan receptor 2 (ROR2) is an essential receptor for Wnt5a, it was reasonable to deduce that ROR2 might be one of the key molecules for the therapeutic effect of MSCs in ARDS. The mMSCs that stably overexpressed ROR2 or the green fluorescent protein (GFP) control were transplanted intratracheally into the ARDS mice [induced by intratracheal injection of lipopolysaccharide (LPS)]. The results showed that ROR2-overexpressing mMSCs led to more significant effects than the GFP controls, including the retention of the mMSCs in the lung, differentiation into AT II cells, improvement of alveolar epithelial permeability, improvement of acute LPS-induced pulmonary inflammation, and, finally, reduction of the pathological impairment of the lung tissue. In conclusion, MSCs that overexpress ROR2 could further improve MSC-mediated protection against epithelial impairment in ARDS.
authors.affiliation: Department of Critical Care Medicine, Nanjing Zhong-da Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Shi-Xia
authors.initials: SX
authors.lastname: Cai
authors.forename: Ai-Ran
authors.initials: AR
authors.lastname: Liu
authors.forename: Song
authors.initials: S
authors.lastname: Chen
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: He
authors.forename: Qi-Hong
authors.initials: QH
authors.lastname: Chen
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Xu
authors.forename: Chun
authors.initials: C
authors.lastname: Pan
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Feng-Mei
authors.initials: FM
authors.lastname: Guo
authors.forename: Ying-Zi
authors.initials: YZ
authors.lastname: Huang
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Qiu
mesh_terms: D055371:Acute Lung Injury / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics / Q000378:metabolism*; D012128:Respiratory Distress Syndrome / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D008070:Lipopolysaccharides; D049452:Green Fluorescent Proteins; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C477010:Ror2 protein, mouse