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Wilczynska, Malgorzata
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Publications (10 of 28) Show all publications
Wielkoszynski, T., Moghaddam, A., Backman, A., Broden, J., Piotrowski, R., Mond-Paszek, R., . . . Wilczynska, M. (2018). Novel diagnostic ELISA test for discrimination between infections with Yersinia enterocolitica and Yersinia pseudotuberculosis. European Journal of Clinical Microbiology and Infectious Diseases, 37(12), 2301-2306
Open this publication in new window or tab >>Novel diagnostic ELISA test for discrimination between infections with Yersinia enterocolitica and Yersinia pseudotuberculosis
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2018 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 37, no 12, p. 2301-2306Article in journal (Refereed) Published
Abstract [en]

Yersiniosis is a foodborne infection caused by Yersinia enterocolitica or Yersinia pseudotuberculosis. Although yersiniosis is most often self-limiting, some patients develop chronic infections, such as reactive arthritis, glomerulonephritis, or myocarditis, which require an antibiotic treatment. Whereas early infections can be diagnosed by direct detection of bacteria, chronic infections can only be identified by serological tests. At this point, a serological method for differentiation between infections with the two Yersinia species is important since antibiotic susceptibility of these bacteria is different. Traditional immunoassays do not distinguish between infections with Y. enterocolitica and Y. pseudotuberculosis. The only test that allows for this differentiation is Mikrogen's strip test where discrimination between the two types of infection is based on two recombinant bacterial proteins, MyfA and PsaA (specific for Y. enterocolitica and Y. pseudotuberculosis, respectively). Here, we show that Y. enterocolitica and Y. pseudotuberculosis, cultured under the conditions that mimic the natural rout of infection, express surface antigens different from MyfA and PsaA that can also be used in a discrimination test. Further, we describe a new ELISA that is based on the whole bacteria and recombinant MyfA and PsaA as antigens, and that allows the differentiation between infections with Y. enterocolitica and Y. pseudotuberculosis and simultaneous detection of yersiniosis.

Place, publisher, year, edition, pages
Springer, 2018
Keywords
Yersinia enterocolitica, Yersinia pseudotuberculosis, Diagnostics, Novel ELISA test, Discrimination between Yersinia species
National Category
Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-154938 (URN)10.1007/s10096-018-3373-9 (DOI)000449921100010 ()30238343 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-01-07Bibliographically approved
Fallah, M., Shen, Y., Brodén, J., Bäckman, A., Lundskog, B., Johansson, M., . . . Ny, T. (2018). Plasminogen activation is required for the development of radiation-induced dermatitis. Cell Death and Disease, 9(11), Article ID 1051.
Open this publication in new window or tab >>Plasminogen activation is required for the development of radiation-induced dermatitis
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2018 (English)In: Cell Death and Disease, ISSN 2041-4889, E-ISSN 2041-4889, Vol. 9, no 11, article id 1051Article in journal (Refereed) Published
Abstract [en]

Skin damage caused by radiation therapy (radiodermatitis) is a severe side effect of radiotherapy in cancer patients, and there is currently a lack of effective strategies to prevent or treat such skin damage. In this work, we show with several lines of evidence that plasminogen, a pro-inflammatory factor, is key for the development of radiodermatitis. After skin irradiation in wild type (plg+/+) mice, the plasminogen level increased in the radiated area, leading to severe skin damage such as ulcer formation. However, plasminogen-deficient (plg−/−) mice and mice lacking plasminogen activators were mostly resistant to radiodermatitis. Moreover, treatment with a plasminogen inhibitor, tranexamic acid, decreased radiodermatitis in plg+/+ mice and prevented radiodermatitis in plg+/ mice. Together with studies at the molecular level, we report that plasmin is required for the induction of inflammation after irradiation that leads to radiodermatitis, and we propose that inhibition of plasminogen activation can be a novel treatment strategy to reduce and prevent the occurrence of radiodermatitis in patients.

 

 

Place, publisher, year, edition, pages
Springer, 2018
Keywords
Inflammation, plasminogen, radiation-induced dermatitis
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-152950 (URN)10.1038/s41419-018-1106-8 (DOI)000447324600005 ()30323258 (PubMedID)
Available from: 2018-10-31 Created: 2018-10-31 Last updated: 2018-11-01Bibliographically approved
Sulniute, R., Shen, Y., Guo, Y.-Z., Fallah, M., Ahlskog, N., Ny, L., . . . Ny, T. (2016). Plasminogen is a critical regulator of cutaneous wound healing. Thrombosis and Haemostasis, 115(5), 1001-1009
Open this publication in new window or tab >>Plasminogen is a critical regulator of cutaneous wound healing
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2016 (English)In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 115, no 5, p. 1001-1009Article in journal (Refereed) Published
Abstract [en]

Wound healing is a complicated biological process that consist of partially overlapping inflammatory, proliferation and tissue remodelling phases. A successful wound healing depends on a proper activation and subsequent termination of the inflammatory phase. The failure to terminate the inflammation halts the completion of wound healing and is a known reason for formation of chronic wounds. Previous studies have shown that wound closure is delayed in plasminogen deficient mice, and a role for plasminogen in dissection of extracellular matrix was suggested. However, our finding that plasminogen is transported to the wound by inflammatory cells early during the healing process, where it potentiates inflammation, indicates that plasminogen may also have other roles in the wound healing process. Here we report that plasminogen-deficient mice have extensive fibrin and neutrophil depositions in the wounded area long after re-epithelialisation, indicating inefficient debridement and chronic inflammation. Delayed formation of granulation tissue suggests that fibroblast function is impaired in the absence of plasminogen. Therefore, in addition to its role in the activation of inflammation, plasminogen is also crucial for subsequent steps, including resolution of inflammation and activation of the proliferation phase. Importantly, supplementation of plasminogen-deficient mice with human plasminogen leads to a restored healing process that is comparable to that in wild-type mice. Besides of being an activator of the inflammatory phase during wound healing, plasminogen is also required for the subsequent termination of inflammation. Based on these results, we propose that plasminogen may be an important future therapeutic agent for wound treatment.

Keywords
Plasminogen, wound healing, inflammation
National Category
Hematology
Identifiers
urn:nbn:se:umu:diva-121571 (URN)10.1160/TH15-08-0653 (DOI)000375372400015 ()
Available from: 2016-06-30 Created: 2016-06-03 Last updated: 2018-10-31Bibliographically approved
Shen, Y., Guo, Y., Wilczynska, M., Li, J., Hellström, S. & Ny, T. (2014). Plasminogen initiates and potentiates the healing of acute and chronic tympanic membrane perforations in mice. Journal of Translational Medicine, 12, Article ID 5.
Open this publication in new window or tab >>Plasminogen initiates and potentiates the healing of acute and chronic tympanic membrane perforations in mice
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2014 (English)In: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, Vol. 12, article id 5Article in journal (Refereed) Published
Abstract [en]

Background: Most tympanic membrane (TM) perforations heal spontaneously, but approximately 10-20% remain open as chronic TM perforations. Chronic perforations can lead to an impaired hearing ability and recurrent middle ear infections. Traditionally, these perforations must be surgically closed, which is costly and time consuming. Therefore, there is a need for simpler therapeutic strategies. Previous studies by us have shown that plasminogen (plg) is a potent pro-inflammatory regulator that accelerates cutaneous wound healing in mice. We have also shown that the healing of TM perforations is completely arrested in plg-deficient (plg(-/-)) mice and that these mice develop chronic TM perforations. In the present study, we investigated the therapeutic potential of local plg injection in acute and chronic TM perforation mice models. Methods: Plg(-/-) mice and wild-type mice were subjected to standardized TM perforations followed by local injection of plg into the soft tissue surrounding the TM. TM perforations with chronic characteristics were induced by leaving TM perforations in plg(-/-) mice untreated for 9 days before treatment. The healing process was observed through otomicroscope and finally confirmed by immunostaining. The quality of TM healing was evaluated based on the morphology of the TM. Result: Daily local injections of plg into the soft tissue surrounding the TM restored the ability to heal TM perforations in plg(-/-) mice in a dose-dependent manner, and potentiated the healing rate and quality in wild-type mice. A single local injection of plg initiated the healing of the chronic-like TM perforations in these mice, resulting in a closed TM with a continuous but rather thick outer keratinocyte layer. However, three plg injections led to a completely healed TM with a thin keratinizing squamous epithelium covering a connective tissue layer. Conclusion: Our data suggests that plg is a promising drug candidate for the treatment of chronic TM perforations in humans.

Place, publisher, year, edition, pages
BioMed Central, 2014
Keywords
Plasminogen, wound healing, tympanic membrane perforations
National Category
Basic Medicine Otorhinolaryngology
Identifiers
urn:nbn:se:umu:diva-68759 (URN)10.1186/1479-5876-12-5 (DOI)000330279900001 ()24393366 (PubMedID)
Funder
Swedish Research Council, B0322301
Available from: 2013-04-25 Created: 2013-04-25 Last updated: 2018-06-08Bibliographically approved
Shen, Y., Guo, Y., Du, C., Wilczynska, M., Hellström, S. & Ny, T. (2012). Mice deficient in urokinase-type plasminogen activator have delayed healing of tympanic membrane perforations. PLoS ONE, 7(12), e51303
Open this publication in new window or tab >>Mice deficient in urokinase-type plasminogen activator have delayed healing of tympanic membrane perforations
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2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 12, p. e51303-Article in journal (Refereed) Published
Abstract [en]

Mice deficient in plasminogen, the precursor of plasmin, show completely arrested healing of tympanic membrane (TM) perforations, indicating that plasmin plays an essential role in TM healing. The activation of plasminogen to plasmin is performed by two plasminogen activators (PAs), urokinase-type PA (uPA) and tissue-type PA (tPA). To elucidate the functional roles of PAs in the healing of TM perforations, we investigated the phenotypes of single gene-deficient mice lacking uPA (uPA(-/-)) or tPA (tPA(-/-)) after TM perforation. Delayed healing of TM perforations was observed in uPA(-/-) mice but not tPA(-/-) mice. The migration of keratinocytes was clearly delayed and seemed to be misoriented in uPA(-/-) mice. Furthermore, fibrin deposition and the inflammatory response were persistent in these mice. Our findings demonstrate that uPA plays a role in the healing of TM perforations. The observed phenotypes in uPA(-/-) mice are most likely due to the reduced generation of plasmin.

Place, publisher, year, edition, pages
Public library of science, 2012
Keywords
receptor; upa; keratinocytes; system; gene; model
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-64176 (URN)10.1371/journal.pone.0051303 (DOI)000312064100090 ()23236466 (PubMedID)
Available from: 2013-01-17 Created: 2013-01-17 Last updated: 2018-06-08Bibliographically approved
Shen, Y., Guo, Y., Mikus, P., Sulniute, R., Wilczynska, M., Ny, T. & Li, J. (2012). Plasminogen is a key proinflammatory regulator that accelerates the healing of acute and diabetic wounds. Blood, 119(24), 5879-5887
Open this publication in new window or tab >>Plasminogen is a key proinflammatory regulator that accelerates the healing of acute and diabetic wounds
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2012 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 119, no 24, p. 5879-5887Article in journal (Refereed) Published
Abstract [en]

Despite decades of research on wound healing, effective biologic agents for the treatment of chronic wounds, especially diabetic wounds, are still lacking. In the present study, we report that the inert plasma protein plasminogen (plg) acts as a key regulatory molecule that potentiates wound healing in mice. Early in the healing process, plg bound to inflammatory cells is transported to the wound area, where the level of plg is increased locally, leading to the induction of cytokines and intracellular signaling events and to a potentiation of the early inflammatory response. Systemic administration of additional plg not only accelerates the healing of acute burn wounds in wild-type mice, but also improves the healing of chronic diabetic wounds in a mouse model of diabetes. Our results suggest that the administration of plg may be a novel therapeutic strategy to treat many different types of wounds, especially chronic wounds such as those caused by diabetes. (Blood. 2012; 119(24):5879-5887)

Place, publisher, year, edition, pages
Washington, USA: American society of hematology, 2012
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-58921 (URN)10.1182/blood-2012-01-407825 (DOI)000307396500041 ()
Available from: 2012-09-07 Created: 2012-09-06 Last updated: 2018-06-08Bibliographically approved
Decker, D., Meng, M., Gornicka, A., Hofer, A., Wilczynska, M. & Kleczkowski, L. A. (2012). Substrate kinetics and substrate effects on the quaternary structure of barley UDP-glucose pyrophosphorylase. Phytochemistry, 79, 39-45
Open this publication in new window or tab >>Substrate kinetics and substrate effects on the quaternary structure of barley UDP-glucose pyrophosphorylase
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2012 (English)In: Phytochemistry, ISSN 0031-9422, E-ISSN 1873-3700, Vol. 79, p. 39-45Article in journal (Refereed) Published
Abstract [en]

UDP-Glc pyrophosphorylase (UGPase) is an essential enzyme responsible for production of UDP-Glc, which is used in hundreds of glycosylation reactions involving addition of Glc to a variety of compounds. In this study, barley UGPase was characterized with respect to effects of its substrates on activity and quaternary structure of the protein. Its K(m) values with Glc-1-P and UTP were 0.33 and 0.25 mM, respectively. Besides using Glc-1-P as a substrate, the enzyme had also considerable activity with Gal-1-P; however, the K(m) for Gal-1-P was very high (>10 mM), rendering this reaction unlikely under physiological conditions. UGPase had a relatively broad pH optimum of 6.5-8.5, regardless of the direction of reaction. The enzyme equilibrium constant was 0.4, suggesting slight preference for the Glc-1-P synthesis direction of the reaction. The quaternary structure of the enzyme, studied by Gas-phase Electrophoretic Mobility Macromolecule Analysis (GEMMA), was affected by addition of either single or both substrates in either direction of the reaction, resulting in a shift from UGPase dimers toward monomers, the active form of the enzyme. The substrate-induced changes in quaternary structure of the enzyme may have a regulatory role to assure maximal activity. Kinetics and factors affecting the oligomerization status of UGPase are discussed.

Keywords
Cell wall synthesis, Oligomerization, Protein structure, Sucrose metabolism, Sucrose synthase, Sugar activation, UDP-sugar synthesis
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-58610 (URN)10.1016/j.phytochem.2012.04.002 (DOI)000307031800003 ()22552276 (PubMedID)
Available from: 2012-09-04 Created: 2012-09-04 Last updated: 2018-06-08Bibliographically approved
Kleczkowski, L. A., Geisler, M., Fitzek, E. & Wilczynska, M. (2011). A common structural blueprint for plant UDP-sugar-producing pyrophosphorylases.. Biochemical Journal, 439(3), 375-379
Open this publication in new window or tab >>A common structural blueprint for plant UDP-sugar-producing pyrophosphorylases.
2011 (English)In: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 439, no 3, p. 375-379Article in journal (Refereed) Published
Abstract [en]

Plant pyrophosphorylases that are capable of producing UDP-sugars, key precursors for glycosylation reactions, include UDP-glucose pyrophosphorylases (A- and B-type), UDP-sugar pyrophosphorylase and UDP-N-acetylglucosamine pyrophosphorylase. Although not sharing significant homology at the amino acid sequence level, the proteins share a common structural blueprint. Their structures are characterized by the presence of the Rossmann fold in the central (catalytic) domain linked to enzyme-specific N-terminal and C-terminal domains, which may play regulatory functions. Molecular mobility between these domains plays an important role in substrate binding and catalysis. Evolutionary relationships and the role of (de)oligomerization as a regulatory mechanism are discussed.

Place, publisher, year, edition, pages
Colchester: Portland Press, 2011
Keywords
oligomerization, protein structure, sugar activation, UDP-sugar synthesis
National Category
Biological Sciences
Identifiers
urn:nbn:se:umu:diva-50323 (URN)10.1042/BJ20110730 (DOI)21992098 (PubMedID)
Available from: 2011-12-06 Created: 2011-12-06 Last updated: 2018-06-08Bibliographically approved
Sulniute, R., Lindh, T., Wilczynska, M., Li, J. & Ny, T. (2011). Plasmin is essential in preventing periodontitis in mice. American Journal of Pathology, 179(2), 819-828
Open this publication in new window or tab >>Plasmin is essential in preventing periodontitis in mice
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2011 (English)In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 179, no 2, p. 819-828Article in journal (Refereed) Published
Abstract [en]

Periodontitis involves bacterial infection, inflammation of the periodontium, degradation of gum tissue, and alveolar bone resorption, which eventually leads to loss of teeth. To study the role of the broad-spectrum protease plasmin in periodontitis, we examined the oral health of plasminogen (Plg)-deficient mice. In wild-type mice, the periodontium was unaffected at all time points studied; in Plg-deficient mice, periodontitis progressed rapidly, within 20 weeks. Morphological study results of Plg-deficient mice revealed detachment of gingival tissue, resorption of the cementum layer, formation of necrotic tissue, and severe alveolar bone degradation. IHC staining showed massive infiltration of neutrophils in the periodontal tissues. Interestingly, doubly deficient mice, lacking both tissue- and urokinase-type plasminogen activators, developed periodontal disease similar to that in Pig-deficient mice; however, mice lacking only tissue- or urokinase-type plasminogen activator remained healthy. Supplementation by injection of Pig-deficient mice with human plasminogen for 10 days led to necrotic tissue absorption, inflammation subsidence, and full regeneration of gum tissues. Notably, there was also partial regrowth of degraded alveolar bone. Taken together, our results show that plasminogen is essential for the maintenance of a healthy periodontium and plays an important role in combating the spontaneous development of chronic periodontitis. Moreover, reversal to healthy status after supplementation of Pig-deficient mice with plasminogen suggests the possibility of using plasminogen for therapy of periodontal diseases. (Am J Pathol 2011, 179:819-828; DOI: 10.1016/j.ajpath.2011.05.003)

Keywords
disease ligneous periodontitis; activator gene-function; osteoblast-like cells; deficient mice; macrophage activation; mediated proteolysis; tissue regeneration; growth; bone; conjunctivitis
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-51497 (URN)10.1016/j.ajpath.2011.05.003 (DOI)000298307200028 ()
Available from: 2012-01-23 Created: 2012-01-23 Last updated: 2018-06-08Bibliographically approved
Kleczkowski, L. A., Decker, D. & Wilczynska, M. (2011). UDP-sugar pyrophosphorylase: a new old mechanism for sugar activation. Plant Physiology, 156(1), 3-10
Open this publication in new window or tab >>UDP-sugar pyrophosphorylase: a new old mechanism for sugar activation
2011 (English)In: Plant Physiology, ISSN 0032-0889, E-ISSN 1532-2548, Vol. 156, no 1, p. 3-10Article in journal (Refereed) Published
Abstract [en]

Recent developments in studies on properties and functions of UDP-sugar pyrophosphorylase (USPase) in metabolism are presented. The protein was characterized from plants and protozoans (Leishmania, Trypanosoma), but apparently it is also present in bacteria. In plants, USPase deficiency leads to male-sterility. USPase produces a variety of UDP-sugars and their analogs required for cell wall biosynthesis as well as for protein and lipid glycosylation, among other functions. Substrate specificity of USPases from different sources is reviewed, and their function/ structure properties are discussed, based on recent crystallization of the protein, with emphasis on common structural blueprint with some other pyrophosphorylases. Some strategies for future research on USPase are discussed.

National Category
Biochemistry and Molecular Biology Botany
Identifiers
urn:nbn:se:umu:diva-41618 (URN)10.1104/pp.111.174706 (DOI)000290207100001 ()21444645 (PubMedID)
Available from: 2011-03-30 Created: 2011-03-30 Last updated: 2018-06-08Bibliographically approved
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