Defense Date


Document Type


Degree Name

Master of Science



First Advisor

S. Murthy Karnam


The contractility of smooth muscle in inflammatory bowel disease and experimental colitis is reduced due to inhibition of neurotransmitter release and a decrease in the response of smooth muscle to contractile agonists. We and others have shown that inflammation induced by TNBS treatment alters the expression and/or activity of signaling molecules involved in the regulation of Ca2+ mobilization, MLC20 phosphorylation and contraction in colonic smooth muscle. Although, thin filament- associated proteins such as calponin, caldesmon, tropomyosin and smoothelin do not directly participate in contraction, they regulate acto-myosin interaction and thus, muscle contraction. Calponin, caldesmon and tropomyosin inhibit actomyosin interaction and the inhibition is relieved upon phosphorylation of these proteins. Recent studies have shown that visceral smooth muscle from smoothelin knockout mice exhibited decreased contraction. However, the effect of inflammation on the expression of thin filament- associated proteins is not known. The aim of the present study is to determine the changes in the expression of calponin, caldesmon, tropomyosin, and smoothelin in colonic circular smooth muscle from TNBS- and DSS-induced colitis in mice. The animals were euthanized on day 3 and a segment of inflamed distal colon was removed. Colonic muscle strips from colitis mice and control mice were dissected for western blot and real-time RT-PCR analysis; contraction was measured by scanning micrometry in cells isolated from the muscle strips. Contraction in response to acetylcholine in muscle cells isolated from colonic muscle strips derived from mice with TNBS colitis was significantly inhibited compared with the response of cells derived from untreated colon or colon treated with ethanol. Expression of α-actin, γ-actin calponin, caldesmon, smoothelin-A and tropomyosin mRNA in muscle strips from TNBS or DSS colitis was significantly increased compared to control animals. Similarly, expression of α-actin, calponin, caldesmon, smoothelin-A and tropomyosin protein as determined by western blot was significantly increased compared to control animals. We conclude that the expression of α-actin, γ -actin calponin, caldesmon, smoothelin-A and tropomyosin is upregulated in colonic circular smooth muscle from TNBS or DSS colitis. Increase in the expression of calponin, caldesmon and tropomyosin, which act to inhibit acto-myosin interaction, could contribute to decrease in smooth muscle contraction.


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