Theses and Dissertations

Issuing Body

Mississippi State University


Stewart, James A., Jr.

Committee Member

Gordon, Donna M.

Committee Member

Meyer, Florencia

Date of Degree


Document Type

Graduate Thesis - Open Access


Biological Sciences

Degree Name

Master of Science


College of Arts and Sciences


Department of Biological Sciences


Type II diabetes mellitus is associated with many detrimental health situations including heart complications. The purpose of this study was to identify a role for PKA-dependent Rap1a signaling in the AGE-RAGE cascade. My hypothesis was Rap1a GTPase increased the downstream effects of AGE-RAGE signaling in diabetes via a PKA-dependent pathway leading to elevated ECM remodeling in the heart. Cardiac fibroblasts were isolated from heterozygous (Het) and diabetic (db/db) mice. To test the hypothesis, gain-ofunction and loss-ofunction treatments were used. PKC-Zeta is known as a major signaling hub that potentially links PKA-dependent and AGE-RAGE signaling cascades so PKC-Zeta inhibition to downregulate PKA-dependent cascade at PKC-Zeta was also used. Results showed a downregulation of signaling markers in the AGE-RAGE cascade when disrupting Rap1a crosstalk at PKC-Zeta. By understanding where the PKA-dependent and AGE-RAGE signaling cascades crosstalk, a new molecular mechanism is understood possibly leading to decreasing remodeling in a diabetic heart.



siRNA||collagen production||RAGE expression||fibroblast differentiation||myofibroblasts||collagen||AGEs||advanced glycation end-products||western blot analysis||cAMP||EPAC