Browsing by Author "Mathew-Steiner, Shomita"

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    Integrin and microtubule crosstalk in the regulation of cellular processes
    (Springer Nature, 2018-11) LaFlamme, Susan E.; Mathew-Steiner, Shomita; Singh, Neetu; Colello-Borges, Diane; Nieves, Bethsaida; Surgery, School of Medicine
    Integrins engage components of the extracellular matrix, and in collaboration with other receptors, regulate signaling cascades that impact cell behavior in part by modulating the cell's cytoskeleton. Integrins have long been known to function together with the actin cytoskeleton to promote cell adhesion, migration, and invasion, and with the intermediate filament cytoskeleton to mediate the strong adhesion needed for the maintenance and integrity of epithelial tissues. Recent studies have shed light on the crosstalk between integrin and the microtubule cytoskeleton. Integrins promote microtubule nucleation, growth, and stabilization at the cell cortex, whereas microtubules regulate integrin activity and remodeling of adhesion sites. Integrin-dependent stabilization of microtubules at the cell cortex is critical to the establishment of apical-basal polarity required for the formation of epithelial tissues. During cell migration, integrin-dependent microtubule stabilization contributes to front-rear polarity, whereas microtubules promote the turnover of integrin-mediated adhesions. This review focuses on this interdependent relationship and its impact on cell behavior and function.
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    Staphylococcus aureus Biofilm Infection Compromises Wound Healing by Causing Deficiencies in Granulation Tissue Collagen
    (Wolters Kluwer, 2020-06) Roy, Sashwati; Santra, Suman; Das, Amitava; Dixith, Sriteja; Sinha, Mithun; Ghatak, Subhadip; Ghosh, Nandini; Banerjee, Pradipta; Khanna, Savita; Mathew-Steiner, Shomita; Das Ghatak, Piya; Blackstone, Britani N.; Powell, Heather M.; Bergdall, Valerie K.; Wozniak, Daniel J; Sen, Chandan K.; Surgery, School of Medicine
    Objective: The objective of this work was to causatively link biofilm properties of bacterial infection to specific pathogenic mechanisms in wound healing. Background: Staphylococcus aureus is one of the four most prevalent bacterial species identified in chronic wounds. Causatively linking wound pathology to biofilm properties of bacterial infection is challenging. Thus, isogenic mutant stains of S. aureus with varying degree of biofilm formation ability was studied in an established preclinical porcine model of wound biofilm infection. Methods: Isogenic mutant strains of S. aureus with varying degree (ΔrexB > USA300 > ΔsarA) of biofilm-forming ability were used to infect full-thickness porcine cutaneous wounds. Results: Compared with that of ΔsarA infection, wound biofilm burden was significantly higher in response to ΔrexB or USA300 infection. Biofilm infection caused degradation of cutaneous collagen, specifically collagen 1 (Col1), with ΔrexB being most pathogenic in that regard. Biofilm infection of the wound repressed wound-edge miR-143 causing upregulation of its downstream target gene matrix metalloproteinase-2. Pathogenic rise of collagenolytic matrix metalloproteinase-2 in biofilm-infected wound-edge tissue sharply decreased collagen 1/collagen 3 ratio compromising the biomechanical properties of the repaired skin. Tensile strength of the biofilm infected skin was compromised supporting the notion that healed wounds with a history of biofilm infection are likely to recur. Conclusion: This study provides maiden evidence that chronic S. aureus biofilm infection in wounds results in impaired granulation tissue collagen leading to compromised wound tissue biomechanics. Clinically, such compromise in tissue repair is likely to increase wound recidivism.