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- Abu Seman, N, et al.
(författare)
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Genetic and biological effects of sodium-chloride cotransporter (SLC12A3) in diabetic nephropathy
- 2014
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 40:5, s. 408-416
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background/Aims:</i></b> Solute carrier family 12 member 3 (<i>SLC12A3</i>) encodes a sodium/chloride transporter in kidneys. Previous reports suggest that Arg913Gln polymorphism in this gene is associated with diabetic nephropathy (DN), but the data appear to be inconsistent. Up to now, there is no biological evidence concerning the effects of <i>SLC12A3</i> in DN. In this study, we aim to evaluate the genetic effects of the <i>SLC12A3 </i>gene and its Arg913Gln polymorphism with genetic and functional analyses. <b><i>Methods:</i></b> We genotyped <i>SLC12A3</i> genetic polymorphisms including Arg913Gln in 784 non-diabetes controls and 633 type 2 diabetes (T2D) subjects with or without DN in a Malaysian population and performed a meta-analysis of the present and previous studies. We further analyzed the role of <i>slc12a3</i> in kidney development and progress of DN in zebrafish and db/db mice. <b><i>Results:</i></b> We found that <i>SLC12A3</i> Arg913Gln polymorphism was associated with T2D (p = 0.028, OR = 0.772, 95% CI = 0.612-0.973) and DN (p = 0.038, OR = 0.547, 95% CI = 0.308-0.973) in the Malaysian cohort. The meta-analysis confirmed the protective effects of <i>SLC12A3</i> 913Gln allele in DN (Z-value = -1.992, p = 0.046, OR = 0.792). Furthermore, with knockdown of zebrafish ortholog, <i>slc12a3 </i>led to structural abnormality of kidney pronephric distal duct at 1-cell stage. <i>Slc12a3</i> mRNA and protein expression levels were upregulated in kidneys of db/db mice from 6, 12, and 26 weeks at the age. <b><i>Conclusion:</i></b> The present study provided the first biological and further genetic evidence that <i>SLC12A3</i> has genetic susceptibility in the development of DN, while the minor 913Gln allele in this gene confers a protective effect in the disease. i 2014 S. Karger AG, Basel
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| 4. |
- Horejs, CM, et al.
(författare)
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Preventing tissue fibrosis by local biomaterials interfacing of specific cryptic extracellular matrix information
- 2017
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8, s. 15509-
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Tidskriftsartikel (refereegranskat)abstract
- Matrix metalloproteinases (MMPs) contribute to the breakdown of tissue structures such as the basement membrane, promoting tissue fibrosis. Here we developed an electrospun membrane biofunctionalized with a fragment of the laminin β1-chain to modulate the expression of MMP2 in this context. We demonstrate that interfacing of the β1-fragment with the mesothelium of the peritoneal membrane via a biomaterial abrogates the release of active MMP2 in response to transforming growth factor β1 and rescues tissue integrity ex vivo and in vivo in a mouse model of peritoneal fibrosis. Importantly, our data demonstrate that the membrane inhibits MMP2 expression. Changes in the expression of epithelial-to-mesenchymal transition (EMT)-related molecules further point towards a contribution of the modulation of EMT. Biomaterial-based presentation of regulatory basement membrane signals directly addresses limitations of current therapeutic approaches by enabling a localized and specific method to counteract MMP2 release applicable to a broad range of therapeutic targets.
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| 6. |
- Ojala, JRM, et al.
(författare)
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A novel scavenger receptor 5-based antibiotic-independent selection method for generation of stable recombinant protein-producing mammalian cell lines especially suitable for proteins affecting cell adhesion
- 2012
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Ingår i: BioTechniques. - : Future Science Ltd. - 1940-9818 .- 0736-6205. ; 53:4, s. 221-
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Tidskriftsartikel (refereegranskat)abstract
- The establishment of stable recombinant protein-producing mammalian cell lines is an expensive, time-consuming, tedious procedure. In some cases, expressed recombinant proteins have adverse effects on host cell function, including cell adhesion. Based on the adhesive properties of SCARA5, a scavenger receptor (SR) of the class A SR family, we developed a method for selection of stable recombinant protein-producing cell clones that relies on an internal ribosome entry site (IRES) vector where the protein of interest is expressed in the same messenger RNA as SCARA5, resulting in improved adhesion and increased cell viability of recombinant protein-producing cells in serum-free media. This method does not depend on antibiotics, complicated selective cell culture media or equipment, and thus offers the advantages of being inexpensive, environmentally friendly, and simple.
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