Thesica.org, the #1 open access web portal for PhD theses...

Why PhD theses...

PhD thesis is the result of years of hard work.

keyword researchMeasured by download count PhD theses are one of the most popular items world wide on open access repositories. But unless a thesis is published, it is very difficult for other researchers to find out about it and get access to it. Theses are often under-used by other researchers. Thesica.org attempts to address this issue by making it easy to identify and locate copies of many theses in various disciplines.

The potential role of a carboxypeptidase B2 inhibitor in renal fibrosis

The potential role of a carboxypeptidase B2 inhibitor in renal fibrosis
Oguntona Taiwo Shola

2018

Department of Infection, Immunity and Cardiovascular Disease, The University of Sheffield, Sheffield, South Yorkshire S10 2TN, UNITED KINGDOM.

ABSTRACT

Diabetic nephropathy (DN) is a fibrotic disease from renal injury which is characterized by extracellular matrix (ECM) build-up. Thus, DN leads to disruption of renal architecture and loss of renal function. We hypothesized that renal fibrosis can be improved by increasing plasmin activity through inhibition of carboxypeptidase B2 (CPB2) activity using UK-396082- a selective CPB2 inhibitor.

An in vivo rat model of DN was used. Unilateral nephrectomy and induction of type 1 diabetes with 80mg/kg streptozotocin injection. Blood glucose was maintained between 20-25 mM for 8 months with linplants. The rats were divided into 3 groups. Group 1 (diseased) fed on normal chow. Group 3 (treatment) fed on normal chow for four months after which it was changed to chow mixed with 0.3g/kg of UK-396082 for the final four months. Group 2 (prophylaxis) fed on chow mixed with a 0.3g/kg of UK- 396082 for 8 month.

In an in vitro study CPB2, plasmin, tissue–type (tPA) and urokinase-type (uPA) plasminogen activators were assayed in the presence and absence of UK-396082 in rat kidney epithelial-like, fibroblast-like and mesangial cells cultured on plastic and fibrin gel.

Our results confirmed DN in this rat model. Prophylactic administration of UK-396082 gave protection against development of kidney fibrosis and impaired kidney function. However, with advanced DN, UK-396082 appeared to have little protective effect. The In vitro results demonstrated that CPB2, tPA, uPA and plasmin activities were present in rat kidney epithelial-like, fibroblast-like and mesangial cell culture. CPB2, tPA, and plasmin activities were increased when epithelial and mesangial rat kidney cells were cultured on fibrin as opposed to plastic.

Both epithelial-like and mesangial cells in the presence of fibrin led to more plasmin generation in the presence of UK-396082.