TY - JOUR
T1 - Impaired intestinal wound healing in Fhl2-deficient mice is due to disturbed collagen metabolism
AU - Kirfel, Jutta
AU - Pantelis, Dimitrios
AU - Kabba, Mustapha
AU - Kahl, Philip
AU - Röper, Anke
AU - Kalff, Jörg C.
AU - Buettner, Reinhard
N1 - Funding Information:
We gratefully acknowledge the technical help of Claudine Neumann and Renate Gammel. We thank G. Klemm for excellent help with the artwork. This work was supported by grants from the DFG to J.K., J.C.K. and R.B.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2008/12/10
Y1 - 2008/12/10
N2 - Four and one half LIM domain protein FHL2 participates in many cellular processes involved in tissue repair such as regulation of gene expression, cytoarchitecture, cell adhesion, migration and signal transduction. The repair process after wounding is initiated by the release of peptides and bioactive lipids. These molecules induce synthesis and deposition of a provisional extracellular matrix. We showed previously that sphingosine-1-phosphate (S1P) triggers a signal transduction cascade mediating nuclear translocation of FHL2 in response to activation of the RhoA GTPase. Our present study shows that FHL2 is an important signal transducer influencing the outcome of intestinal anastomotic healing. Early wound healing is accompanied by reconstitution and remodelling of the extracellular matrix and collagen is primarily responsible for wound strength. Our results show that impaired intestinal wound healing in Fhl2-deficient mice is due to disturbed collagen III metabolism. Impaired collagen III synthesis reduced the mechanical stability of the anastomoses and led to lower bursting pressure in Fhl2-deficient mice after surgery. Our data confirm that FHL2 is an important factor regulating collagen expression in the early phase of wound healing, and thereby is critically involved in the physiologic process of anastomosis healing after bowel surgery and thus may represent a new therapeutic target.
AB - Four and one half LIM domain protein FHL2 participates in many cellular processes involved in tissue repair such as regulation of gene expression, cytoarchitecture, cell adhesion, migration and signal transduction. The repair process after wounding is initiated by the release of peptides and bioactive lipids. These molecules induce synthesis and deposition of a provisional extracellular matrix. We showed previously that sphingosine-1-phosphate (S1P) triggers a signal transduction cascade mediating nuclear translocation of FHL2 in response to activation of the RhoA GTPase. Our present study shows that FHL2 is an important signal transducer influencing the outcome of intestinal anastomotic healing. Early wound healing is accompanied by reconstitution and remodelling of the extracellular matrix and collagen is primarily responsible for wound strength. Our results show that impaired intestinal wound healing in Fhl2-deficient mice is due to disturbed collagen III metabolism. Impaired collagen III synthesis reduced the mechanical stability of the anastomoses and led to lower bursting pressure in Fhl2-deficient mice after surgery. Our data confirm that FHL2 is an important factor regulating collagen expression in the early phase of wound healing, and thereby is critically involved in the physiologic process of anastomosis healing after bowel surgery and thus may represent a new therapeutic target.
UR - http://www.scopus.com/inward/record.url?scp=56249096177&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2008.09.023
DO - 10.1016/j.yexcr.2008.09.023
M3 - Journal articles
C2 - 18950620
AN - SCOPUS:56249096177
VL - 314
SP - 3684
EP - 3691
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 20
ER -