Method for evaluating and/or screening a control agent for tissue morphology and/or tissue function

1 . A method for evaluating and/or screening a control agent for skin morphology and/or skin function, the method comprising:

applying a test substance to a continuous tension-homeostatic skin model comprising artificial dermis comprising normal human fibroblasts dispersed in a gel and capable of expressing a mechanical stress signaling molecule to identify a candidate substance; and

evaluating expression, activity, or intracellular localization of the mechanical stress signaling molecule in the tension-homeostatic skin model, wherein the mechanical stress signaling molecule is at least one selected from the group consisting of ITGA2 (integrin alpha 2), MRTFA (myocardin-related transcription factor A), and ACTA2 (actin alpha 2).

2 . The method according to claim 1 , wherein, in the evaluating step, expression, activity, or intracellular localization of the mechanical stress signaling molecule is compared with a control.

3 . The method according to claim 2 , wherein the control is said tension-homeostatic skin model but with no test substance applied or only a solvent of the test substance applied.

4 . The method according to claim 1 , wherein the continuous tension-homeostatic skin model comprises a tension-related artificial dermis comprising normal human dermis fibroblasts and normal human epidermal keratinocytes.

5 . The method according to claim 1 , wherein said artificial dermis is prepared by dispersing and seeding normal human dermis fibroblasts in a gel, solidifying said gel, fixing the solidified gel in a culture vessel to apply continuous tension, and further seeding normal epidermal keratinocytes on said solidified gel.

6 . The method according to claim 1 , which further comprises subjecting said candidate substance identified by said evaluating step to further screening to confirm whether said candidate substance enhances, reduces, or otherwise alters the expression level, activity, or localization of said mechanical stress signaling molecule.

7 . A method for evaluating and/or screening a control agent for skin morphology and/or skin function, the method comprising:

applying a test substance to a tissue or cells taken from a mammal selected from skin tissue, epidermal tissue, dermis tissue, epidermal cells, or dermis cells, a culture of said tissue or cells, and a continuous tension homeostatic skin model composed of any of these capable of expressing a mechanical stress signaling molecule to identify a candidate substance; and

evaluating expression, activity, or intracellular localization of the mechanical stress signaling molecule in the tension-homeostatic skin model,

wherein the mechanical stress signaling molecule is at least one selected from the group consisting of ITGA2 (integrin alpha 2), MRTFA (myocardin-related transcription factor A), and ACTA2 (actin alpha 2).

8 . The method according to claim 7 , wherein the test substance is applied to epidermal keratinocytes.

9 . The method according to claim 7 , wherein the test substance is applied to dermal fibroblasts.

10 . The method according to claim 7 , wherein the test substance is applied to said established cell line of said tissue or cells.

11 . The method according to claim 7 , wherein, in the evaluating step, expression, activity, or intracellular localization of the mechanical stress signaling molecule is compared with a control group.

12 . The method according to claim 11 , wherein the control group include those having the same tissue or cell as that of the test group but with no test substance applied or only a solvent of the test substance applied.

13 . The method according to claim 7 , which further comprises subjecting said candidate substance identified by said evaluating step to further screening to confirm whether said candidate substance enhances, reduces, or otherwise alters the expression level, activity, or localization of said mechanical stress signaling molecule.