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Persistent disruption of lateral junctional complexes and actin cytoskeleton in parotid salivary glands following radiation treatment
Author(s) -
Wong Wen Yu,
Pier Maricela,
Limesand Kirsten H.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.869.4
Subject(s) - adherens junction , microbiology and biotechnology , actin cytoskeleton , cytoskeleton , actin , cadherin , biology , cancer research , cell , biochemistry
Xerostomia and hyposalivation are debilitating side effects for patients treated with ionizing radiation for head and neck cancer. Despite technological advances, collateral damage to the salivary glands remains a significant problem for patients and severely diminishes their quality of life. During the wound healing process, restoration of junctional contacts is necessary to maintain polarity, structural integrity, and orientation cues for secretion. However, little is known about whether these structural molecules are impacted following radiation damage and more importantly following tissue restoration. Here, we evaluated changes in adherens junctions and cytoskeletal regulators in an injury model where mice were irradiated with 5 Grey (5Gy) and a restoration model where mice injected post‐radiation with insulin like growth factor 1 (IGF1) are capable of restoring salivary function. Using co‐immunoprecipitation, we determined that there is a decrease in β‐catenin bound to E‐cadherin following damage that is restored to untreated levels with IGF1. Via its adaptor proteins, β‐catenin links the cadherins to the cytoskeleton and part of this regulation is mediated through Rho‐associated coiled‐coil kinase (ROCK) signaling. In our model, F‐actin organization is also disrupted and there is an induction of ROCK activity. These findings illustrate that radiation induces a disruption of the cadherin‐catenin complex, alters F‐actin organization, and induces ROCK signaling at early and chronic stages where salivary hyposalivation is observed. Understanding the role of these components and its regulation may be important in tissue restoration where a coordinated and polarized epithelium are necessary for functionality. Support or Funding Information This work was supported in part by NIH R01 DE023534 received by Kirsten Limesand and stipend support for Wen Yu Wong was provided by the Cancer Biology Training Grant, T32CA009213‐38 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .