Consistent with how decreased meprin
activity relates to kidney injury, we recently showed that meprin
ap double knockout mice exhibit more severe kidney injury upon streptozotocin-induced type 1 diabetes .
a and meprin
fi: procollagen proteinases in health and disease," Matrix Biology, vol.
Abbreviations BTB: Bric-a-brac, tramtrack, and broad complex ZF: Zinc finger BACK: BTB and C-terminal Kelch MATH: Meprin
and TRAF homology ANK: Ankyrin Rho: Ras homology BR-C: Broad complex.
The team at Penn State College of Medicine along with colleagues from Switzerland studied the role of meprin
in IBD using genetically altered mice lacking the ability to produce it.
We compared wild-type (WT) and meprin
[alpha][beta] knockout ([alpha][beta]KO) mice in which the genes for both meprin
a and meprin
S were disrupted.
Human B-type natriuretic peptide is not degraded by meprin
Twelve-week-old wild-type and meprin
[alpha] [beta] double knockout ([alpha][beta]KO) mice on a C57BL/6 background were used for these studies.
Successive action of meprin
A and neprilysin catabolizes B-type natriuretic peptide.
The GLP-1-independent effects have been associated with other known substrates of DPP-4, such as high mobility group box 1 protein (HMGB1), meprin
[beta], neuropeptide Y (NPY), and peptide YY (PYY) [76, 164].
The bioactive BNP 1-32 is further processed by receptors or enzymes like neprilysin, dipeptidyl peptidase IV, insulin degrading enzyme, meprin
, and potentially other enzymatic pathways which may be identified in the future (4-6).
We first used high-dose STZ (100mg/kg body weight for 2 days) to determine whether diabetes affects meprin
There are data showing that, in mice, meprin
A, a protease expressed in kidney, may increase the effect of neprilysin by cleaving the first 6 N-terminal residues of mouse BNP (29).
Previously, assays for novel biomarkers such as caveolin-1, irisin, meprin
A, and filimin B have not been commercially available; however, kits for the measurement of hundreds of such analytes in humans, dog, horse, mouse, rat, cow, monkey, pig, and a variety of other species can now be purchased from distributors in the US, Europe, and other parts of the world.
The vast majority of the inactivation was abolished in boiled membranes, consistent with a proteolytic-dependent mechanism, and neither the neutral endo-peptidase inhibitor, phosphoramidon, nor the meprin
inhibitor, actinonin, blocked inactivation (Fig.
[2.] Sterchi EE, Stocker W, Bond JS (2008) Meprins
, membrane-bound and secreted astacin metalloproteinase.