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Up‐Regulated p38, PCNA, and Decreased Smooth Muscle Actin in Cyclophilin C‐Associated Protein Null Mice During Skin Wound Healing
Author(s) -
Kong Wuyi,
Peter Lorenz H.
Publication year - 2008
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1067-1927.2005.130215ar.x
Subject(s) - wound healing , proliferating cell nuclear antigen , microbiology and biotechnology , p38 mitogen activated protein kinases , fibronectin , biology , signal transduction , mapk/erk pathway , immunology , immunohistochemistry , extracellular matrix
Cyclophilin C‐associated protein (CyC‐AP) expression is up‐regulated during wound healing. CyC‐AP deletion causes greater expression of TNFα, MMP‐3, MMP‐13, and MMP‐14 during cutaneous repair. Furthermore, CyC‐AP is a mediator for fibronectin‐fragment induced MMP‐13 expression. In order to understand the effects of the deletion of CyC‐AP at the cellular level, we investigated the intracellular signal transduction pathways of CyC‐AP null and wild‐type mice during skin wound healing. Methods: Two‐month‐old CyC‐AP null or wild‐type mice were anesthetized and two 0.6 cm diameter excisional skin wounds were made on the dorsum of each mouse. Wounds were collected up to 10 days after injury. Total protein was purified from each wound and the protein expression of TNFα converting enzyme (TACE), integrin beta 1, ERK 1, ERK 2, p38, PCNA, and smooth muscle actin (sm‐actin) was analyzed by immunoblot. Results: TNFα expression was higher in CyC‐AP null mice in unwounded skin. However, the elevated TNFα in CyC‐AP null wounds was lower compared to the wild‐type mice. To further understand the relationship of CyC‐AP and TNFα, TACE expression was examined. TACE expression was less in the skin of CyC‐AP null mice compared to wild‐type mice. Expression of p38 and PCNA increased while sm‐actin decreased in both unwounded and wounded CyC‐AP null skin compared to wild type. PCNA expression in CyC‐AP null fibroblasts was also higher compared to wild type, supporting our in vivo observations. In addition, the expression of integrin beta 1 was lower during wound healing. Conclusion: The increased PCNA and decreased sm‐actin expression suggests that CyC‐AP null fibroblasts have higher proliferation and lower differentiation rates compared to wild types. These effects might be regulated through the p38 signaling pathway, which was increased in CyC‐AP null mice. The decreased TACE expression in CyC‐AP null skin suggests CyC‐AP may also regulate TACE via the altered expression of integrin beta 1. Our data suggest CyC‐AP is involved in TNFα activation.