Publication Date

2010-02-18

Availability

Open access

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Molecular Cell and Developmental Biology (Medicine)

Date of Defense

2009-03-11

First Committee Member

Theodore Lampidis - Committee Chair

Second Committee Member

Vinata Lokeshwar - Committee Member

Third Committee Member

TK Harris - Committee Member

Fourth Committee Member

Kermit Carraway - Mentor

Abstract

MUC4 is a heterodimeric mucin glycoprotein expressed in the epithelia of tissues. Previous studies in our laboratory demonstrated that MUC4 protein expression is regulated by exogenous growth factors and that MUC4 is found in complex with the receptor tyrosine kinase ErbB2. MUC4 protein expression in airway epithelia was evaluated using molecular biology techniques. The impact of the protein on ErbB2 activation was evaluated post mechanical wounding of airway epithelia, and upon MUC4 RNA silencing. MUC4 levels were increased with exposure to the differentiating agent retinoic acid and decreased upon exposure to epidermal growth factor, a proliferative agent. In the absence of MUC4, ErbB2 phosphorylation was diminished. These results support the hypothesis that MUC4 expression is enhanced during differentiation of epithelia. Furthermore these findings provide evidence for an additional level of ErbB regulation in airway injury and subsequent epithelial wound healing.

Keywords

Mucin; SMC; MUC4; ErbB2; Airway Epithelia; Growth Factors; Mechanical Injury

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