title: Roles of Wnt/β-catenin signaling in retinal neuron-like differentiation of bone marrow mesenchymal stem cells from nonobese diabetic mice.
abstract: Recent studies have shown that mesenchymal stem cells (MSCs) are expected to become promising therapeutic agents for the treatment of diabetic retinopathy (DR); moreover, we previously demonstrated that bone marrow (BM)-MSCs from nonobese diabetic (NOD) mice (an ideal DR model) had abnormal migration and adhesion. So, we hypothesized that NOD-MSCs also have abnormal retinal neuron-like differentiation potential. MSCs were cultured with brain-derived neurotrophic factor, nerve growth factor, and basic fibroblast growth factor. Western blot analysis and immunofluorescence both showed that the level of retinal neuron-like markers, such as glial fibrillary acidic protein, neuron-specific nuclear protein, tyrosine hydroxylase, Thy-1, glutamine synthetase, and rhodopsin was lower in NOD-MSCs than in imprinting control region MSCs. Furthermore, we explored the precise mechanisms controlling this change in NOD-MSCs. The expression levels of some important member proteins in Wnt/β-catenin signaling were determined and suggested the downregulation of Wnt/β-catenin signaling with retinal neuron-like differentiation of NOD-MSCs. Incubation of NOD-MSCs in medium supplemented with human recombinant Wnt1 resulted in a significant upregulation of retinal neuron-like markers, and the effects of Wnt1 were dose-dependent. Taken together, our study indicated that the inhibition of Wnt/β-catenin signaling in NOD-MSCs after induction could contribute to the abnormal retinal neuron-like differentiation. These data provide important preclinical references supporting the basis for further development of autologous MSC-based therapies for DR.
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yue
authors.affiliation: Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
authors.forename: Gu
authors.initials: G
authors.lastname: Zhifeng
authors.affiliation: Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
authors.forename: Shen
authors.initials: S
authors.lastname: Biyu
authors.affiliation: Department of Internal Medicine, Affiliated Changzhou No. 5 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu Province 223000, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Guofeng
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Tianqiu
authors.affiliation: Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Jinxia
authors.affiliation: Department of Gastroenterology and Hepatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
authors.forename: Xing
authors.initials: X
authors.lastname: Jing
authors.affiliation: Department of Gastroenterology and Hepatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
authors.forename: Liu
authors.initials: L
authors.lastname: Suzhe
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Man
authors.affiliation: Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
authors.forename: Tan
authors.initials: T
authors.lastname: Wei
authors.affiliation: Department of Gastroenterology and Hepatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Guijuan
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
authors.forename: Sang
authors.initials: S
authors.lastname: Aimin
authors.affiliation: Department of Gastroenterology and Hepatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Liren
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002454:Cell Differentiation; D005260:Female; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005786:Gene Expression Regulation; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000166:cytology*; D051379:Mice; D016688:Mice, Inbred NOD; D020932:Nerve Growth Factor / Q000494:pharmacology; D055351:Retinal Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D051153:Wnt Proteins; D051176:beta Catenin; D005346:Fibroblast Growth Factors; D020932:Nerve Growth Factor