Frontiers of Chemical Science and Engineering >
Mechanisms of connective tissue formation and blocks of mitogen activated protein kinase
Received date: 20 Nov 2011
Accepted date: 27 Feb 2012
Published date: 05 Jun 2012
Copyright
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.
Key words： connective tissue; mitogen activated protein kinase (MAPK); p38; JNK
Irina A SHURYGINA , Michael G SHURYGIN , Nataliya I AYUSHINOVA , Galina B GRANINA , Nikolay V ZELENIN . Mechanisms of connective tissue formation and blocks of mitogen activated protein kinase[J]. Frontiers of Chemical Science and Engineering, 2012 , 6(2) : 232 -237 . DOI: 10.1007/s11705-012-1286-1
| 1 |
Pearson G, Robinson F, Beers Gibson T, Xu B E, Karandikar M, Berman K, Cobb M H. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocrine Reviews, 2001, 22(2): 153–183
|
| 2 |
Oltmanns U, Issa R, Sukkar M B, John M, Chung K F. Role of c-jun N-terminal kinase in the induced release of GM-CSF, RANTES and IL-8 from human airway smooth muscle cells. British Journal of Pharmacology, 2003, 139(6): 1228–1234
|
| 3 |
de Boer W I. Perspectives for cytokine antagonist therapy in COPD. Drug Discovery Today, 2005, 10(2): 93–106
|
| 4 |
Cheng Y, Prusoff W H. Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochemical Pharmacology, 1973, 22(23): 3099–3108
|
| 5 |
Davies S P, Reddy H, Caivano M, Cohen P. Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochemical Journal, 2000, 351(Pt 1): 95–105
|
| 6 |
Wang Y, Ji H X, Xing S H, Pei D S, Guan Q H. SP600125, a selective JNK inhibitor, protects ischemic renal injury via suppressing the extrinsic pathways of apoptosis. Life Sciences, 2007, 80(22): 2067–2075
|
| 7 |
Shurygin M G, Dremina N N, Shurygina I A, Machkhin I N, Antipina S L. RU Patent, <patent>2332665</patent>, 2008-08-27
|
| 8 |
Glantz S A, Slinker B K. Primer of applied regression and analysis of variance. New York: McGraw-Hill / Appleton & Lange, 2000, 949
|
| 9 |
Boutros T, Chevet E, Metrakos P. Mitogen-activated protein (MAP) kinase/MAP kinase phosphatase regulation: roles in cell growth, death, and cancer. Pharmacological Reviews, 2008, 60(3): 261–310
|
/
| 〈 |
|
〉 |