KD025 (SLx-2119) suppresses adipogenesis at intermediate stage in human adipose-derived stem cells
Rho-associated kinases (ROCKs) have been reported to antagonize adipocyte differentiation, and inhibition of ROCKs by small molecules promotes adipogenesis. Surprisingly, our recent study revealed that the ROCK2-specific inhibitor KD025 (SLx-2119), suppresses differentiation at the intermediate stag...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-01-01
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| Series: | Adipocyte |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21623945.2019.1590929 |
| _version_ | 1818544677750571008 |
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| author | Duy Trong Vien Diep Khue Ha Minh Duong Hojung Choi Hee-Sook Jun Kwang-Hoon Chun |
| author_facet | Duy Trong Vien Diep Khue Ha Minh Duong Hojung Choi Hee-Sook Jun Kwang-Hoon Chun |
| author_sort | Duy Trong Vien Diep |
| collection | DOAJ |
| description | Rho-associated kinases (ROCKs) have been reported to antagonize adipocyte differentiation, and inhibition of ROCKs by small molecules promotes adipogenesis. Surprisingly, our recent study revealed that the ROCK2-specific inhibitor KD025 (SLx-2119), suppresses differentiation at the intermediate stage in 3T3-L1 preadipocytes. To address whether the anti-adipogenic activity of KD025 is a generalizable property, we examined the effect of KD025 in human adipose-derived stem cells (hADSCs). KD025 significantly suppressed the adipocyte differentiation of hADSCs with downregulation of the protein and mRNA expression of various adipogenic and lipogenic markers, including PPARγ, C/EBPα, SREBP-1c, Glut4 and FABP4. Notably, we observed that adipocyte differentiation is effectively suppressed by exposure to KD025 during the mid-to-late period of adipogenesis but not at the earlier stages, showing stage-specificity. Contrary to expectations, KD025 upregulated the insulin signaling, as confirmed by the increased phosphorylation levels of Akt and GSK-3α/β, and the differentiation-promoting activity of insulin signaling was observed to be overwhelmed by the inhibitory activity. In addition, we observed that other ROCK inhibitors (Y-27632, fasudil, and H-1152P) did not suppress but promoted adipocyte differentiation. These results indicate that KD025 suppresses adipocyte differentiation by modulation of key factors activated at the intermediate stage of differentiation, and not by inhibition of ROCK2. |
| first_indexed | 2024-12-11T22:51:34Z |
| format | Article |
| id | doaj.art-39e39f5cb9c3476aa29a1826041717a1 |
| institution | Directory Open Access Journal |
| issn | 2162-3945 2162-397X |
| language | English |
| last_indexed | 2024-12-11T22:51:34Z |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Adipocyte |
| spelling | doaj.art-39e39f5cb9c3476aa29a1826041717a12022-12-22T00:47:25ZengTaylor & Francis GroupAdipocyte2162-39452162-397X2019-01-018111412410.1080/21623945.2019.15909291590929KD025 (SLx-2119) suppresses adipogenesis at intermediate stage in human adipose-derived stem cellsDuy Trong Vien Diep0Khue Ha Minh Duong1Hojung Choi2Hee-Sook Jun3Kwang-Hoon Chun4Gachon UniversityGachon UniversityGachon UniversityGachon UniversityGachon UniversityRho-associated kinases (ROCKs) have been reported to antagonize adipocyte differentiation, and inhibition of ROCKs by small molecules promotes adipogenesis. Surprisingly, our recent study revealed that the ROCK2-specific inhibitor KD025 (SLx-2119), suppresses differentiation at the intermediate stage in 3T3-L1 preadipocytes. To address whether the anti-adipogenic activity of KD025 is a generalizable property, we examined the effect of KD025 in human adipose-derived stem cells (hADSCs). KD025 significantly suppressed the adipocyte differentiation of hADSCs with downregulation of the protein and mRNA expression of various adipogenic and lipogenic markers, including PPARγ, C/EBPα, SREBP-1c, Glut4 and FABP4. Notably, we observed that adipocyte differentiation is effectively suppressed by exposure to KD025 during the mid-to-late period of adipogenesis but not at the earlier stages, showing stage-specificity. Contrary to expectations, KD025 upregulated the insulin signaling, as confirmed by the increased phosphorylation levels of Akt and GSK-3α/β, and the differentiation-promoting activity of insulin signaling was observed to be overwhelmed by the inhibitory activity. In addition, we observed that other ROCK inhibitors (Y-27632, fasudil, and H-1152P) did not suppress but promoted adipocyte differentiation. These results indicate that KD025 suppresses adipocyte differentiation by modulation of key factors activated at the intermediate stage of differentiation, and not by inhibition of ROCK2.http://dx.doi.org/10.1080/21623945.2019.1590929kd025slx-2119adipogenesisdifferentiationrockrho-associated kinase |
| spellingShingle | Duy Trong Vien Diep Khue Ha Minh Duong Hojung Choi Hee-Sook Jun Kwang-Hoon Chun KD025 (SLx-2119) suppresses adipogenesis at intermediate stage in human adipose-derived stem cells Adipocyte kd025 slx-2119 adipogenesis differentiation rock rho-associated kinase |
| title | KD025 (SLx-2119) suppresses adipogenesis at intermediate stage in human adipose-derived stem cells |
| title_full | KD025 (SLx-2119) suppresses adipogenesis at intermediate stage in human adipose-derived stem cells |
| title_fullStr | KD025 (SLx-2119) suppresses adipogenesis at intermediate stage in human adipose-derived stem cells |
| title_full_unstemmed | KD025 (SLx-2119) suppresses adipogenesis at intermediate stage in human adipose-derived stem cells |
| title_short | KD025 (SLx-2119) suppresses adipogenesis at intermediate stage in human adipose-derived stem cells |
| title_sort | kd025 slx 2119 suppresses adipogenesis at intermediate stage in human adipose derived stem cells |
| topic | kd025 slx-2119 adipogenesis differentiation rock rho-associated kinase |
| url | http://dx.doi.org/10.1080/21623945.2019.1590929 |
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