Mechanisms of connective tissue formation and blocks of mitogen activated protein kinase

Abstract

Ninety male Wistar rats were selected under the “Guide for the Care and Use of Laboratory Animals” for skin-muscle wound models. Three groups of animals were examined respectively for inoculation of inhibitor of p38 MAPK (mitogen activated protein kinase) SB 203580 and JNK inhibitor SP 600125, and a control. Light microscopy, immunohistochemistry, and tensometry revealed that the inhibition of p38 or JNK cascades have modified the formation of the connective tissue scar. The degree of connective tissue growth in the area of surgical wound had been significantly reduced by the end of observation (30 d) as the SB 203580 was applied (% volume of collagen 43.60 (41.05 – 60.15) vs. 73.54 (66.87 – 78.01) in control, p = 0.002). Conversely, when we have applied the JNK blocker, the density of collagen in scar tissue increased (78.14 (72.77 – 81.14), p = 0.022 vs. control). SB203580 inhibits the expression of p38, c-Jun and c-Fos. When we have used the JNK blocker, the expression of c-Fos and c-Jun decreased, but the expression of p38 increased. This determines the high functional activity of fibroblasts after using SP 600125. Obtained results show the importance of studying regulators of cell differentiation as potential drugs, which significantly affect the outcome of the pathological processes.

Keywords

connective tissue / mitogen activated protein kinase (MAPK) / p38 / JNK

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Acknowledgments

This work was supported by the Ministry of Education and Science of the Russian Federation.

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg