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  • A motivation for this study is the ability of

    2021-11-29

    A motivation for this study is the ability of PGD2 to inhibit hair lengthening (). Here we demonstrate that PGD2 also inhibits hair regeneration after wounding. Thus, PGD2 and Gpr44 inhibition of the hair follicle occurs in multiple contexts and may be exploited in future therapies. Pharmaceutical companies are already focused on the development of Gpr44-selective antagonists for the treatment of 1,3-PBIT dihydrobromide receptor with at least nine other known Gpr44 antagonists in phase II clinical trials (; Norman, 2010; Pettipher and Whittaker, 2012). In addition to previous studies suggesting that Gpr44 antagonists may be beneficial in androgenetic alopecia, our results suggest that formulations of Gpr44 antagonists may decrease scarring during wound healing. A specific example is ramatroban, an orally active, dual Gpr44, and thromboxane A2 receptor antagonist, which is approved in Japan for the treatment of allergic rhinitis in humans (). Future studies could examine the effect of ramatroban in stimulating hair follicle neogenesis.
    MATERIALS AND METHODS
    ACKNOWLEDGMENTS
    Introduction Diabetes mellitus types 1 and 2 (T1D and T2D) are caused by destruction and dysfunction of the insulin-producing beta cells in the pancreas. To address questions regarding onset and progression of both T1D and T2D, and to evaluate effects of various treatment modalities, it is important to be able to distinguish between alterations in beta cell function and beta cell mass. For that purpose, a beta cell-specific marker that fulfills several requirements is needed: Firstly, the low quantity of beta cell mass in comparison to the exocrine tissue in the pancreas requires at least a 100 fold higher retention of a tracer in the beta cells when compared to that in exocrine cells [1]. Secondly, human islets contain an equal number of other endocrine cells, in addition to beta cells that are required to be negative for the target. Thirdly, the target should preferentially be expressed at the cell surface to enable in vivo detection. Insulin is the only true tissue-specific marker of beta cells that so far has been identified. However, since insulin is a cytoplasmic protein it cannot be used for imaging of beta cells. In addition, insulin expression reflects the function of beta cells and not necessarily the mass of the beta cells. Several molecules have been tested as possible targets for beta cell assessment, but so far no ideal target has been found that fulfills all requirements [2], [3]. The most promising radiotracer for positron emission tomography (PET) imaging of beta cells is dihydrotetrabenzine that targets the vesicular monoamine transporter type 2 (VMAT2). However, in patients with long-standing T1D a decrease of only about 15% in VMAT2 binding was observed, when compared to normal controls [4]. Another well characterized target on beta cells is the glucagon-like peptide 1 receptor (GLP-1R). Recently, Reiner et al. reported that an analogue to the GLP-1R ligand exendin-4, accurately measured beta cell mass in mice [5]. GLP-1R is however, expressed in other abdominal organs besides the pancreas [6] which could result in interference with beta cell imaging. To enable accurate measurements of the beta cell mass in patients, more specific surface biomarkers are required. Antibody-based proteomics provides a strategy to explore protein expression patterns on a genome-wide scale [7]. Based on such a strategy, the Human Protein Atlas (HPA) project has been set up to generate antibodies towards at least one major isoform of all human proteins encoded by the human genome. The produced and validated antibodies are further used to map protein expression patterns in normal tissues, cancer tissues and cell lines, using immunofluorescence and immunohistochemistry [8], [9]. At present, data and images representing over 12,200 unique proteins, corresponding to approximately 60% of all human protein encoding genes are publically available on the HPA portal (http://www.proteinatlas.org) [10]. This database allows for queries of proteins expressed in specified cell types and is thus an attractive starting point to identify potential biomarkers [11], [12]. In the present investigation, the HPA database was used to identify proteins with strong and selective expression in islets of Langerhans while no expression in pancreatic exocrine cells or cells in abdominal organs close to the pancreas. The twelve most promising candidate proteins were selected for further studies with the aim to investigate their specificity for beta cells.