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The Role of Hyaluronan Size in Murine Asthma

Rodgers, Jennifer Leigh

Abstract Details

2016, Doctor of Philosophy in Clinical-Bioanalytical Chemistry, Cleveland State University, College of Sciences and Health Professions.
Hyaluronan (HA), a component of extracellular matrix (ECM), helps maintains tissue integrity and regulates water homeostasis. HA is a high molecular weight (HMW) polymer of repeated D-glucuronic acid and N-acetyl-D-glucosamine disaccharides exceeding 106 Daltons in mass. ECM turnover results in accumulation of HA fragments of lower molecular weight (LMW). Asthma is a chronic lung disease, characterized by inflammation, airway hyperresponsiveness (AHR), airway remodeling, and ECM turnover. HA is elevated in asthmatics as has been found correlate with disease severity, but its role in asthma is not well understood. In this study, we utilized two models of murine asthma to provide evidence that treatment with HA impacted AHR in vivo, mediated by interleukin-13 (IL-13), a Th2 cytokine. IL-13 is strongly linked to development of the asthmatic phenotype, including AHR. In our study, we treated mice intratracheally with either LMW or HMW HA in either an ovalbumin (OVA) or house dust mite (HDM) model of antigen-induced murine asthma. While both HA sizes impacted AHR in our OVA model, only HMW HA significantly impacted AHR in our HDM model. The observed increase in AHR in both models correlated to increased mRNA expression of IL-13 within the lung. In an in vitro model, airway epithelial cells (AECs) treated with either LMW or HMW HA demonstrated significantly elevated levels of certain Th2 cytokines, and SAA3. We propose that our observed results in vivo are linked to HA signaling in AECs.
Mark Aronica, Ph.D. (Advisor)
Aimin Zhou, Ph.D. (Committee Member)
Yan Xu, Ph.D. (Committee Member)
David Anderson, Ph.D. (Committee Member)
Vincent Hascall, Ph.D. (Committee Member)
164 p.

Recommended Citations

Citations

  • Rodgers, J. L. (2016). The Role of Hyaluronan Size in Murine Asthma [Doctoral dissertation, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1464261240

    APA Style (7th edition)

  • Rodgers, Jennifer. The Role of Hyaluronan Size in Murine Asthma. 2016. Cleveland State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1464261240.

    MLA Style (8th edition)

  • Rodgers, Jennifer. "The Role of Hyaluronan Size in Murine Asthma." Doctoral dissertation, Cleveland State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=csu1464261240

    Chicago Manual of Style (17th edition)