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Functional characterization of human Kindlin-2 core promoter identifies a key role of SP1 in Kindlin-2 transcriptional regulation

100%

Khan A., Shimokawa T., Stromblad S., Zhang H.

Cellular and Molecular Biology Letters

2011

tom 16

nr 4

Kindlin-2 is a recently identified FERM and PH domain containing integrin interacting protein. Kindlin-2 is ubiquitously expressed in normal tissues. So far, much effort has been spent exploring the functional aspects of Kindlin-2. However, the transcriptional regulation of Kindlin-2 has not yet been investigated. In this study we identified and functionally characterized the promoter of the human Kindlin-2 gene. We show that the core promoter of Kindlin-2 is a 39 base pair long GC rich fragment located −122/-83 upstream of the Kindlin-2 transcription start site. Functional characterization of this core promoter region by both in silico as well as in vitro/in vivo analysis shows that the transcription factor SP1 plays an important role in regulation of Kindlin-2 expression.

Rho kinase inhibitors stimulate the migration of human cultured osteoblastic cells by regulating actomyosin activity

64%

Zhang X., Li C., Gao H., Nabeka H., Shimokawa T., Wakisaka H., Matsuda S., Kobayashi N.

Cellular and Molecular Biology Letters

2011

tom 16

nr 2

We investigated the effects of Rho-associated kinase (ROCK) on migration and cytoskeletal organization in primary human osteoblasts and Saos-2 human osteosarcoma cells. Both cell types were exposed to two different ROCK inhibitors, Y-27632 and HA-1077. In the improved motility assay used in the present study, Y-27632 and HA-1077 significantly increased the migration of both osteoblasts and osteosarcoma cells on plastic in a dose-dependent and reversible manner. Fluorescent images showed that cells of both types cultured with Y-27632 or HA-1077 exhibited a stellate appearance, with poor assembly of stress fibers and focal contacts. Western blotting showed that ROCK inhibitors reduced myosin light chain (MLC) phosphorylation within 5 min without affecting overall myosin light-chain protein levels. Inhibition of ROCK activity is thought to enhance the migration of human osteoblasts through reorganization of the actin cytoskeleton and regulation of myosin activity. ROCK inhibitors may be potentially useful as anabolic agents to enhance the biocompatibility of bone and joint prostheses.

Ograniczanie wyników

2 Cellular and Molecular Biology Letters

2 Shimokawa T.

1 Gao H.

1 Khan A.

1 Kobayashi N.

1 Li C.

1 Matsuda S.

1 Nabeka H.

1 Stromblad S.

1 Wakisaka H.

1 Zhang H.

1 Zhang X.

2 2011

Wyniki wyszukiwania

Functional characterization of human Kindlin-2 core promoter identifies a key role of SP1 in Kindlin-2 transcriptional regulation

Rho kinase inhibitors stimulate the migration of human cultured osteoblastic cells by regulating actomyosin activity