The Antiaging Gene Klotho Regulates Proliferation and Differentiation of Adipose-Derived Stem Cells
Autor: | Zhongjie Sun, Jun Fan |
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Rok vydání: | 2016 |
Předmět: |
Pluripotent Stem Cells
0301 basic medicine Homeobox protein NANOG Aging medicine.medical_specialty Cellular differentiation Peroxisome proliferator-activated receptor Biology urologic and male genital diseases Article Transforming Growth Factor beta1 Mice 03 medical and health sciences Internal medicine medicine Animals Induced pluripotent stem cell Klotho Proteins Klotho Cell Proliferation Glucuronidase chemistry.chemical_classification Adipogenesis Stem Cells Cell Differentiation Cell Biology female genital diseases and pregnancy complications Recombinant Proteins Cell biology 030104 developmental biology Endocrinology Adipose Tissue chemistry Molecular Medicine Signal transduction Stem cell Signal Transduction Transcription Factors Developmental Biology |
Zdroj: | Stem Cells. 34:1615-1625 |
ISSN: | 1549-4918 1066-5099 |
Popis: | Klotho was originally discovered as an aging-suppressor gene. The purpose of this study was to investigate whether secreted Klotho (SKL) affects the proliferation and differentiation of adipose-derived stem cells (ADSCs). RT-PCR and Western blot analysis showed that short-form Klotho was expressed in mouse ADSCs. The Klotho gene mutation KL(–/–) significantly decreased proliferation of ADSCs and expression of pluripotent transcription factors (Nanog, Sox-2, and Oct-4) in mice. The adipogenic differentiation of ADSCs was also decreased in KL(–/–) mice. Incubation with Klotho-deficient medium decreased ADSC proliferation, pluripotent transcription factor levels, and adipogenic differentiation, which is similar to what was found in KL(–/–) mice. These results indicate that Klotho deficiency suppresses ADSC proliferation and differentiation. Interestingly, treatment with recombinant SKL protein rescued the Klotho deficiency-induced impairment in ADSC proliferation and adipogenic differentiation. SKL also regulated ADSCs' differentiation to other cell lineages (osteoblasts, myofibroblasts), indicating that SKL maintains stemness of ADSCs. It is intriguing that overexpression of SKL significantly increased PPAR-γ expression and lipid formation in ADSCs following adipogenic induction, indicating enhanced adipogenic differentiation. Overexpression of SKL inhibited expression of TGFβ1 and its downstream signaling mediator Smad2/3. This study demonstrates, for the first time, that SKL is essential to the maintenance of normal proliferation and differentiation in ADSCs. Klotho regulates adipogenic differentiation in ADSCs, likely via inhibition of TGFβ1 and activation of PPAR-γ. |
Databáze: | OpenAIRE |
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