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miR-125a-3p and miR-483-5p promote adipogenesis via suppressing the RhoA/ROCK1/ERK1/2 pathway in multiple symmetric lipomatosis.

Chen K, He H, Xie Y, Zhao L, Zhao S, Wan X, Yang W, Mo Z - Sci Rep (2015)

Bottom Line: Most importantly, we found that miR-125a-3p and miR-483-5p promoted de novo adipose tissue formation in nude mice.These results demonstrated that miR-125a-3p and miR-483-5p coordinately promoted adipogenesis through suppressing the RhoA/ROCK1/ERK1/2 pathway.Our findings may provide novel strategies for the management and treatment of MSL or obesity.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, China.

ABSTRACT
Multiple symmetric lipomatosis (MSL) is a rare disease characterized by symmetric and abnormal distribution of subcutaneous adipose tissue (SAT); however, the etiology is largely unknown. We report here that miR-125a-3p and miR-483-5p are upregulated in the SAT of MSL patients, promoting adipogenesis through suppressing the RhoA/ROCK1/ERK1/2 pathway. TaqMan microRNA (miR) array analysis revealed that 18 miRs were upregulated in the SAT of MSL patients. Transfection of human adipose-derived mesenchymal stem cells (hADSCs) with the individual agomirs of these 18 miRs showed that miR-125a-3p and miR-483-5p significantly promoted adipogenesis. A dual-luciferase assay showed that RhoA and ERK1 were the targets of miR-125a-3p and miR-483-5p, respectively. Moreover, transfection of hADSCs with mimics of miR-125a-3p and miR-483-5p resulted in a pronounced decrease of ERK1/2 phosphorylation in the nucleus; conversely, transfection of hADSCs with inhibitors of miR-125a-3p and miR-483-5p led to a significant increase of ERK1/2 phosphorylation in the nucleus. Most importantly, we found that miR-125a-3p and miR-483-5p promoted de novo adipose tissue formation in nude mice. These results demonstrated that miR-125a-3p and miR-483-5p coordinately promoted adipogenesis through suppressing the RhoA/ROCK1/ERK1/2 pathway. Our findings may provide novel strategies for the management and treatment of MSL or obesity.

No MeSH data available.


Related in: MedlinePlus

A proposed model of the regulation of adipogenesis by miR-125a-3p and miR-483-5p.In hADSCs, miR-125a-3p inhibits RhoA, resulting in decreased ROCK1 expression, which inhibits n-T-ERK1/2 and n-p-ERK1/2 in the nucleus. At the same time, miR-483-5p directly decreases T-ERK1/2 and T-p-ERK1/2 in the cytoplasm, and n-T-ERK1/2 and n-p-ERK1/2 in the nucleus. Subsequently, PPARγ, a downstream target of n-T-ERK1/2 and n-p-ERK1/2, which are negatively correlated with PPARγ, is increased and promotes adipogenesis.
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f7: A proposed model of the regulation of adipogenesis by miR-125a-3p and miR-483-5p.In hADSCs, miR-125a-3p inhibits RhoA, resulting in decreased ROCK1 expression, which inhibits n-T-ERK1/2 and n-p-ERK1/2 in the nucleus. At the same time, miR-483-5p directly decreases T-ERK1/2 and T-p-ERK1/2 in the cytoplasm, and n-T-ERK1/2 and n-p-ERK1/2 in the nucleus. Subsequently, PPARγ, a downstream target of n-T-ERK1/2 and n-p-ERK1/2, which are negatively correlated with PPARγ, is increased and promotes adipogenesis.

Mentions: In this study, we discovered that 18 miRs were upregulated in the SAT of MSL patients and that miR-125a-3p or miR-483-5p significantly promoted adipogenesis via the RhoA/ROCK1/ERK1/2 pathway (Fig. 7). Importantly, we found that miR-125a-3p and miR-483-5p promoted de novo adipose tissue formation in nude mice. These results demonstrated that miRs play an important role during adipogenesis and could be used in potential novel strategies for the prevention and treatment of MSL or obesity.


miR-125a-3p and miR-483-5p promote adipogenesis via suppressing the RhoA/ROCK1/ERK1/2 pathway in multiple symmetric lipomatosis.

Chen K, He H, Xie Y, Zhao L, Zhao S, Wan X, Yang W, Mo Z - Sci Rep (2015)

A proposed model of the regulation of adipogenesis by miR-125a-3p and miR-483-5p.In hADSCs, miR-125a-3p inhibits RhoA, resulting in decreased ROCK1 expression, which inhibits n-T-ERK1/2 and n-p-ERK1/2 in the nucleus. At the same time, miR-483-5p directly decreases T-ERK1/2 and T-p-ERK1/2 in the cytoplasm, and n-T-ERK1/2 and n-p-ERK1/2 in the nucleus. Subsequently, PPARγ, a downstream target of n-T-ERK1/2 and n-p-ERK1/2, which are negatively correlated with PPARγ, is increased and promotes adipogenesis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493643&req=5

f7: A proposed model of the regulation of adipogenesis by miR-125a-3p and miR-483-5p.In hADSCs, miR-125a-3p inhibits RhoA, resulting in decreased ROCK1 expression, which inhibits n-T-ERK1/2 and n-p-ERK1/2 in the nucleus. At the same time, miR-483-5p directly decreases T-ERK1/2 and T-p-ERK1/2 in the cytoplasm, and n-T-ERK1/2 and n-p-ERK1/2 in the nucleus. Subsequently, PPARγ, a downstream target of n-T-ERK1/2 and n-p-ERK1/2, which are negatively correlated with PPARγ, is increased and promotes adipogenesis.
Mentions: In this study, we discovered that 18 miRs were upregulated in the SAT of MSL patients and that miR-125a-3p or miR-483-5p significantly promoted adipogenesis via the RhoA/ROCK1/ERK1/2 pathway (Fig. 7). Importantly, we found that miR-125a-3p and miR-483-5p promoted de novo adipose tissue formation in nude mice. These results demonstrated that miRs play an important role during adipogenesis and could be used in potential novel strategies for the prevention and treatment of MSL or obesity.

Bottom Line: Most importantly, we found that miR-125a-3p and miR-483-5p promoted de novo adipose tissue formation in nude mice.These results demonstrated that miR-125a-3p and miR-483-5p coordinately promoted adipogenesis through suppressing the RhoA/ROCK1/ERK1/2 pathway.Our findings may provide novel strategies for the management and treatment of MSL or obesity.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, China.

ABSTRACT
Multiple symmetric lipomatosis (MSL) is a rare disease characterized by symmetric and abnormal distribution of subcutaneous adipose tissue (SAT); however, the etiology is largely unknown. We report here that miR-125a-3p and miR-483-5p are upregulated in the SAT of MSL patients, promoting adipogenesis through suppressing the RhoA/ROCK1/ERK1/2 pathway. TaqMan microRNA (miR) array analysis revealed that 18 miRs were upregulated in the SAT of MSL patients. Transfection of human adipose-derived mesenchymal stem cells (hADSCs) with the individual agomirs of these 18 miRs showed that miR-125a-3p and miR-483-5p significantly promoted adipogenesis. A dual-luciferase assay showed that RhoA and ERK1 were the targets of miR-125a-3p and miR-483-5p, respectively. Moreover, transfection of hADSCs with mimics of miR-125a-3p and miR-483-5p resulted in a pronounced decrease of ERK1/2 phosphorylation in the nucleus; conversely, transfection of hADSCs with inhibitors of miR-125a-3p and miR-483-5p led to a significant increase of ERK1/2 phosphorylation in the nucleus. Most importantly, we found that miR-125a-3p and miR-483-5p promoted de novo adipose tissue formation in nude mice. These results demonstrated that miR-125a-3p and miR-483-5p coordinately promoted adipogenesis through suppressing the RhoA/ROCK1/ERK1/2 pathway. Our findings may provide novel strategies for the management and treatment of MSL or obesity.

No MeSH data available.


Related in: MedlinePlus