Date of Award


Document Type

Honors Thesis

Degree Name

Bachelor of Science


Biological Science

Advisor/Committee Chair

Melinda Larsen

Committee Member

Gabriele Fuchs


Fibrosis is characterized by the excessive buildup of extracellular matrix components (ECM) in tissues and organs in response to injury, chronic inflammation, auto immune disorders, and genetic alterations. Non-obese diabetic mice (NOD) are a model for Sjögren’s Syndrome. We hypothesize that NOD mice, which start to develop Sjögren’s-like disease at approximately 12 weeks of age are suffering from hyposalivation at least in part due to fibrosis of the submandibular salivary glands (SMGs). Fibrosis refers to the over-production of extracellular matrix proteins in the connective tissue compartment. To test this hypothesis 16-week-old mice were treated with either the fibrosis inhibitor Nintedanib (treatment) or vehicle (non-treatment) as a negative control for 4 or 8 weeks and compared to an untreated C57BL/6 background strain mouse. The SMGs were then removed and cryopreserved. Histological, serial sections were created to allow for characterization of the entire gland. Masson’s Trichrome staining was performed on cryopreserved sections of the left salivary gland of non-obese diabetic (NOD) mice and control mice to characterize where collagen is deposited as trichrome staining detects fibrillar collagens and elastin. These were compared with salivary glands of NOD mice treated with or without Nintedanib to determine whether there was a reduction in fibrosis. In this study, H&E staining was used to determine where infiltrates were found in the WT, NOD, and Nintedanib-treated mouse tissue sections from the salivary glands. These stained sections were imaged using a brightfield microscope and the number of infiltrates were quantified to determine if Nintedanib decreased infiltrates in the ECM in the salivary glands of NOD compared to the controls. These studies will provide insights into the contribution of ECM deposition on salivary gland hypofunction and inform development of therapeutics for salivary hypofunction.

Included in

Biology Commons