Expression of Laminin γ2 Proteolytic Fragments in Murine Skin Following Exposure to Sulfur Mustard

Published on Jun 1, 2020in Anatomical Record-advances in Integrative Anatomy and Evolutionary Biology1.634
· DOI :10.1002/AR.24405
Yoke Chen Chang3
Estimated H-index: 3
(RU: Rutgers University),
James D. Wang2
Estimated H-index: 2
(RU: Rutgers University)
+ 5 AuthorsDonald R. Gerecke18
Estimated H-index: 18
(RU: Rutgers University)
Sources
Abstract
: Laminin-332 is a basement membrane protein composed of three genetically distinct polypeptide chains that actively promote both skin epidermal cell adhesion and migration. Proteolytic fragments of the laminin γ2 chain stimulate migration and scattering of keratinocytes and cancer cells. Sulfur mustard (SM) is a bifunctional alkylating agent that induces separation of basal keratinocytes from the dermal-epidermal junction and invokes a strong inflammatory response leading to delayed wound repair. In the present studies, the role of laminin γ2 in SM-induced skin injury and wound repair was investigated using the mouse ear vesicant model. We found that laminin γ2 chain mRNA was preferentially upregulated in mouse ear skin exposed to SM. In situ hybridization confirmed overexpression of laminin γ2 transcript. Western blot analysis showed increased protein expression of the full-length proform of laminin γ2 and smaller processed fragments of laminin γ2 in skin exposed to SM. Dual immunofluorescence labeling indicated that laminin γ2 fragments are prevalent in suprabasal keratinocytes behind the leading edge in areas of hyperplasia in injured skin. In addition, co-expression of laminin γ2 and the senescent marker, p16-INK4a was found to overlap with the hyperplastic migratory epithelial sheet. This observation is similar to hypermotile keratinocytes reported in invasive carcinoma cells. Overall, our studies indicate that laminin γ2 is preferentially expressed in skin post SM exposure and that protein expression appears to become progressively more fragmented. The laminin γ2 fragments may play a role in regulating SM-induced skin wound repair. Anat Rec, 2020. © 2020 American Association for Anatomy.
📖 Papers frequently viewed together
6 Authors (N V Kalmykova, ..., Pinaev Gp)
2 Citations
2 Citations
148 Citations
References59
Newest
#1Hiroshi Yasuda (St. Marianna University School of Medicine)H-Index: 21
#1Hiroshi Yasuda (St. Marianna University School of Medicine)H-Index: 8
Last. Motoharu Seiki (UTokyo: University of Tokyo)H-Index: 114
view all 8 authors...
Laminin (Ln)-332 consists of α3, β3, and γ2 chains, which mediate epithelial cell adhesion to the basement membrane. Ln-γ2, a component of Ln-332, is frequently expressed as a monomer in the invasion front of several types of malignant tissues without simultaneous expression of Ln-α3 and/or Ln-β3 chains. Moreover, monomeric Ln-γ2 induces tumor cell proliferation and migration in vitro. These unique biological activities indicate that monomeric Ln-γ2 could be a candidate biomarker for early cance...
8 CitationsSource
#1Patricia Rousselle (University of Lyon)H-Index: 43
#2Marine Montmasson (University of Lyon)H-Index: 2
Last. Cécile Garnier (University of Lyon)H-Index: 1
view all 3 authors...
Abstract The ability of skin to act as a barrier is primarily determined by cells that maintain the continuity and integrity of skin and restore it after injury. Cutaneous wound healing in adult mammals is a complex multi-step process that involves overlapping stages of blood clot formation, inflammation, re-epithelialization, granulation tissue formation, neovascularization, and remodeling. Under favorable conditions, epidermal regeneration begins within hours after injury and takes several day...
69 CitationsSource
#1Yoke Chen Chang (RU: Rutgers University)H-Index: 3
#2Melannie Soriano (RU: Rutgers University)H-Index: 1
Last. Donald R. Gerecke (RU: Rutgers University)H-Index: 18
view all 7 authors...
Abstract Sulfur mustard (2,2′-dichlorodiethyl sulfide, SM) is a chemical warfare agent that generates an inflammatory response in the skin and causes severe tissue damage and blistering. In earlier studies, we identified cutaneous damage induced by SM in mouse ear skin including edema, erythema, epidermal hyperplasia and microblistering. The present work was focused on determining if SM-induced injury was associated with alterations in mRNA and protein expression of specific cytokines and chemok...
5 CitationsSource
#1Satyanarayana Achanta (Duke University)H-Index: 8
#2Narendranath Reddy Chintagari (Yale University)H-Index: 1
Last. Sven-Eric Jordt (Duke University)H-Index: 31
view all 5 authors...
Abstract The skin is highly sensitive to the chemical warfare agent in mustard gas, sulfur mustard (SM) that initiates a delayed injury response characterized by erythema, inflammation and severe vesication (blistering). Although SM poses a continuing threat, used as recently as in the Syrian conflict, no mechanism-based antidotes against SM are available. Recent studies demonstrated that Transient Receptor Potential Ankyrin 1 (TRPA1), a chemosensory cation channel in sensory nerves innervating ...
12 CitationsSource
#1Yoke-Chen Chang (RU: Rutgers University)H-Index: 7
#2Marion K. Gordon (RU: Rutgers University)H-Index: 21
Last. Donald R. Gerecke (RU: Rutgers University)H-Index: 18
view all 3 authors...
Sulfur Mustard (SM) is a potent vesicant or blistering agent. It is a highly reactive bi-functional alkylating agent that cross links proteins, DNA, and other cellular components. Laminin 332 is a heterotrimer glycoprotein and a crucial skin component that attaches the epidermal basal keratinocytes to the dermis. SM wounds histologically appear similar to Epidermolysis Bullosa (EB), human genetic blistering diseases that involve genetic changes in laminin 332. The specific mechanism of action of...
3 Citations
#1Tobias Hirsch (RUB: Ruhr University Bochum)H-Index: 24
#2Tobias Rothoeft (RUB: Ruhr University Bochum)H-Index: 7
Last. Michele De LucaH-Index: 48
view all 26 authors...
Autologous transgenic epidermal stem cell cultures are used to reconstitute almost the entire epidermis of a patient with severe junctional epidermolysis bullosa.
328 CitationsSource
The epidermis is a self-renewing tissue. The balance between proliferation and differentiation processes is tightly regulated to ensure the maintenance of the stem cell (SC) population in the epidermis during life. Aging and cancer may be considered related endpoints of accumulating damages within epidermal self-renewing compartment. p16INK4a is a potent inhibitor of the G1/S-phase transition of the cell cycle. p16INK4a governs the processes of SC self-renewal in several tissues and its deregula...
27 CitationsSource
#1Mariaceleste Aragona (ULB: Université libre de Bruxelles)H-Index: 11
#2Sophie Dekoninck (ULB: Université libre de Bruxelles)H-Index: 10
Last. Cédric Blanpain (ULB: Université libre de Bruxelles)H-Index: 82
view all 7 authors...
Wound healing is essential to repair the skin after injury and distinct stem cells in the epidermis are known to contribute to the process. Here the authors perform molecular, functional and clonal analysis and reveal the individual contribution of stem cells coming from different epidermal compartments to the wound-healing process in mice.
143 CitationsSource
#1Stéphane MouretH-Index: 15
#2Julien WartelleH-Index: 5
Last. Isabelle BoudryH-Index: 9
view all 11 authors...
Sulfur mustard (SM) is a strong bifunctional alkylating agent that produces severe tissue injuries characterized by erythema, edema, subepidermal blisters and a delayed inflammatory response after cutaneous exposure. However, despite its long history, SM remains a threat because of the lack of effective medical countermeasures as the molecular mechanisms of these events remain unclear. This limited number of therapeutic options results in part of an absence of appropriate animal models. We propo...
19 CitationsSource
#1Yoke-Chen Chang (RU: Rutgers University)H-Index: 7
#2James D. Wang (RU: Rutgers University)H-Index: 2
Last. Donald R. Gerecke (RU: Rutgers University)H-Index: 18
view all 13 authors...
Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme med...
18 CitationsSource
Cited By1
Newest
: The idea and meetings that planned this issue focused on extracellular matrix (ECM) started over 4 years ago. The invitations were sent to investigators over 2 years ago and manuscripts have been submitted, reviewed, and edited since the summer and fall of 2018. Most of the manuscripts were published in early view in 2019, and we are thrilled to share the final collection. This volume contains 6 reviews, 13 original research papers, and 4 remembrances. Marion (Emmy) Gordon and I organized the ...
1 CitationsSource