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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

The expression of miR-125a-3p and miR-483-5p are increased with the induction of hADSCs.(A) The hADSCs were induced to mature adipocytes for 12 days. The miR-125a-3p and miR-483-5p expression levels were detected by quantitative real-time PCR at days 0, 6, and 12. (B) The hADSCs were induced to mature adipocytes for 12 days. Total protein was extracted for immunoblotting of RhoA, ROCK1, total ERK1/2 (T-EKR1/2), and phosphorylated ERK1/2 (T-p-EKR1/2) by western blot. (C) The expression of RhoA, ROCK1, T-EKR1/2, and T-p-EKR1/2 in the adipose tissues of MSL patients (n = 3) and controls (n = 3) were determined by western blot. *p < 0.05, **p < 0.01 in comparison to relative expression levels at day 0.
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f4: The expression of miR-125a-3p and miR-483-5p are increased with the induction of hADSCs.(A) The hADSCs were induced to mature adipocytes for 12 days. The miR-125a-3p and miR-483-5p expression levels were detected by quantitative real-time PCR at days 0, 6, and 12. (B) The hADSCs were induced to mature adipocytes for 12 days. Total protein was extracted for immunoblotting of RhoA, ROCK1, total ERK1/2 (T-EKR1/2), and phosphorylated ERK1/2 (T-p-EKR1/2) by western blot. (C) The expression of RhoA, ROCK1, T-EKR1/2, and T-p-EKR1/2 in the adipose tissues of MSL patients (n = 3) and controls (n = 3) were determined by western blot. *p < 0.05, **p < 0.01 in comparison to relative expression levels at day 0.

Mentions: To investigate the expression tendency of miR-125a-3p and miR-483-5p during hADSC differentiation, we used real-time PCR to detect the miR-125a-3p and miR-483-5p expression at days 0, 6, and 12 during the induction to mature adipocytes. Relative to day 0, approximately 3-4- and 4-6-fold increases of miR-125a-3p and miR-483-5p expression were observed at day 6 and day 12 (Fig. 4A), respectively. Similarly, RhoA, ROCK1, and T-p-ERK1/2 were gradually downregulated with the induction time of hADSCs, however, T-ERK1/2 had no change (Fig. 4B). We further assessed the target gene expression in the SAT of the MSL patients and found that RhoA, ROCK1, T-ERK1/2, and T-p-ERK1/2 were all downregulated in the MSL patients compared to that of the controls (Fig. 4C). These results imply that miR-125a-3p and miR-483-5p may play an important role in MSL adipogenesis.


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)

The expression of miR-125a-3p and miR-483-5p are increased with the induction of hADSCs.(A) The hADSCs were induced to mature adipocytes for 12 days. The miR-125a-3p and miR-483-5p expression levels were detected by quantitative real-time PCR at days 0, 6, and 12. (B) The hADSCs were induced to mature adipocytes for 12 days. Total protein was extracted for immunoblotting of RhoA, ROCK1, total ERK1/2 (T-EKR1/2), and phosphorylated ERK1/2 (T-p-EKR1/2) by western blot. (C) The expression of RhoA, ROCK1, T-EKR1/2, and T-p-EKR1/2 in the adipose tissues of MSL patients (n = 3) and controls (n = 3) were determined by western blot. *p < 0.05, **p < 0.01 in comparison to relative expression levels at day 0.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: The expression of miR-125a-3p and miR-483-5p are increased with the induction of hADSCs.(A) The hADSCs were induced to mature adipocytes for 12 days. The miR-125a-3p and miR-483-5p expression levels were detected by quantitative real-time PCR at days 0, 6, and 12. (B) The hADSCs were induced to mature adipocytes for 12 days. Total protein was extracted for immunoblotting of RhoA, ROCK1, total ERK1/2 (T-EKR1/2), and phosphorylated ERK1/2 (T-p-EKR1/2) by western blot. (C) The expression of RhoA, ROCK1, T-EKR1/2, and T-p-EKR1/2 in the adipose tissues of MSL patients (n = 3) and controls (n = 3) were determined by western blot. *p < 0.05, **p < 0.01 in comparison to relative expression levels at day 0.
Mentions: To investigate the expression tendency of miR-125a-3p and miR-483-5p during hADSC differentiation, we used real-time PCR to detect the miR-125a-3p and miR-483-5p expression at days 0, 6, and 12 during the induction to mature adipocytes. Relative to day 0, approximately 3-4- and 4-6-fold increases of miR-125a-3p and miR-483-5p expression were observed at day 6 and day 12 (Fig. 4A), respectively. Similarly, RhoA, ROCK1, and T-p-ERK1/2 were gradually downregulated with the induction time of hADSCs, however, T-ERK1/2 had no change (Fig. 4B). We further assessed the target gene expression in the SAT of the MSL patients and found that RhoA, ROCK1, T-ERK1/2, and T-p-ERK1/2 were all downregulated in the MSL patients compared to that of the controls (Fig. 4C). These results imply that miR-125a-3p and miR-483-5p may play an important role in MSL adipogenesis.

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