Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28270508
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Biol+Chem
2017 ; 292
(16
): 6633-6643
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Discoidin domain receptor 2 mediates collagen-induced activation of membrane-type
1 matrix metalloproteinase in human fibroblasts
#MMPMID28270508
Majkowska I
; Shitomi Y
; Ito N
; Gray NS
; Itoh Y
J Biol Chem
2017[Apr]; 292
(16
): 6633-6643
PMID28270508
show ga
Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a membrane-bound MMP that
is highly expressed in cells with invading capacity, including fibroblasts and
invasive cancer cells. However, pathways of MT1-MMP up-regulation are not clearly
understood. A potential physiological stimulus for MT1-MMP expression is
fibrillar collagen, and it has been shown that it up-regulates both MT1-MMP gene
and functions in various cell types. However, the mechanisms of collagen-mediated
MT1-MMP activation and its physiological relevance are not known. In this study,
we identified discoidin domain receptor 2 (DDR2) as a crucial receptor that
mediates this process in human fibroblasts. Knocking down DDR2, but not the ?1
integrin subunit, a common subunit for all collagen-binding integrins, inhibited
the collagen-induced MT1-MMP-dependent activation of pro-MMP-2 and up-regulation
of MT1-MMP at the gene and protein levels. Interestingly, DDR2 knockdown or
pharmacological inhibition of DDR2 also inhibited the MT1-MMP-dependent cellular
degradation of collagen film, suggesting that cell-surface collagen degradation
by MT1-MMP involves DDR2-mediated collagen signaling. This DDR2-mediated
mechanism is only present in non-transformed mesenchymal cells as
collagen-induced MT1-MMP activation in HT1080 fibrosarcoma cells and MT1-MMP
function in MDA-MB231 breast cancer cells were not affected by DDR kinase
inhibition. DDR2 activation was found to be noticeably more effective when cells
were stimulated by collagen without the non-helical telopeptide region compared
with intact collagen fibrils. Furthermore, DDR2-dependent MT1-MMP activation by
cartilage was found to be more efficient when the tissue was partially damaged.
These data suggest that DDR2 is a microenvironment sensor that regulates
fibroblast migration in a collagen-rich environment.