Sex as a Biological Variable in Pulmonary Fibroblast Mechanical Responses

Abstract

Idiopathic pulmonary fibrosis (IPF) is a terminal lung disease characterized by stiff scar formation in the diseased tissue. It is currently known that males are more susceptible to contract IPF and also tend to have a worse prognosis than females, but the cause of this is unknown. In the diseased tissue, pulmonary fibroblasts become over-activated, causing an excessive production of extracellular matrix (ECM) and contributing to the increased stiffness. These mechanically active cells contract within the ECM when activated and pull on their environment. Pulmonary fibroblasts were isolated from pig lung tissue and encapsulated in 3D collagen hydrogels to compare the contractility of male fibroblasts to females. The hydrogel diameters were measured approximately every 24 hours over 7 days of culture. Males were found to be significantly more contractile in baseline culture conditions. The fibroblasts were also subjected to a TGF-β1 stimulus, a potent growth factor influencing ECM production that is over-expressed in the disease tissue. Males were found to have a significantly greater response to TGF-β1 at the 24 hour time point. Results indicate that the disparity in IPF prognosis between males and females may be due to a difference in fibroblast activation and response to TGF-β1.