Development and Characterization of an In Vitro Model for Radiation-Induced Fibrosis

• DOI: 10.1667/rr14926.1
• Publication Date: 2018-01-19T21:00:11Z
• Authors: Dhruv Kumar; Sreeya Yalamanchali; Jacob New; Sean Parsel; Natalie New; Andrew Holcomb; Sumedha Gunewardena; Ossama Tawfik; Chris Lominska; Bruce F. Kimler; Shrikant Anant; Kiran Kakarala; Terance Tsue; Yelizaveta Shnayder; Kevin Sykes; Subhash Padhye; Sufi Mary Thomas
• Keywords: Integrins; 0303 health sciences; Curcumin; Hepatocyte Growth Factor; Fibroblasts; Fibrosis; Extracellular Matrix; 3. Good health; 03 medical and health sciences; Gene Expression Regulation; Cell Movement; Transforming Growth Factor beta; Humans; Collagen; Pentoxifylline; Radiation Injuries; Cell Proliferation

Radiation-induced fibrosis (RIF) is a major side effect of radiotherapy in cancer patients with no effective therapeutic options. RIF involves excess deposition and aberrant remodeling the extracellular matrix (ECM) leading to stiffness tissues organ failure. Development preclinical models crucial elucidate molecular mechanisms regulating develop approaches. In addition radiation, main perpetrators fibrotic reactions are cytokines, including transforming growth factor-β (TGF-β). We hypothesized that human oral fibroblasts would an vitro reaction response radiation TGF-β. demonstrate here exposed followed by TGF-β exhibit phenotype increased collagen deposition, cell proliferation, migration invasion. this model (RIFiv), early biological processes involved demonstrated, along levels several molecules 1α1, XIα1, integrin-α2 cyclin D1 mRNA irradiated cells. A clinically relevant antifibrotic agent, pentoxifylline, curcumin analogue both mitigated fibroblast cultures. summary, we have established for facilitates elucidation radiation-induced development