RATIONALE TGF-β, a mediator of pulmonary fibrosis, is a genetic modifier of CF respiratory deterioration. The mechanistic relationship between TGF-β signaling and CF lung disease has not been determined. OBJECTIVE To investigate myofibroblast differentiation in CF lung tissue as a novel pathway by which TGF-β signaling may contribute to pulmonary decline, airway remodeling and tissue fibrosis...

PURPOSE TGFbeta is the major mediator to induce myofibroblast differentiation in the corneal wound-healing process. Elevated cAMP can reduce TGFbeta-induced fibrosis in other tissues. This study was conducted to determine whether elevated cAMP can inhibit TGFbeta1-induced rabbit corneal keratocyte-myofibroblast transformation. METHODS Primary isolated rabbit corneal keratocytes were cultured ...

Extracellular vesicles (EVs), such as exosomes and microvesicles, encapsulate proteins and microRNAs (miRNAs) as new modulators of both intercellular crosstalk and disease pathogenesis. The composition of EVs is modified by various triggers to maintain physiological homeostasis. In response to cigarette smoke exposure, the lungs develop emphysema, myofibroblast accumulation and airway remodelli...

Recent studies from our group suggest that extracellular matrix (ECM) deposition and fibrosis characterize the peri-urethral prostate tissues of some men suffering from Lower Urinary Tract Symptoms (LUTS) and that fibrosis may be a contributing factor to the etiology of LUTS. Fibrosis can generally be regarded as an errant wound-healing process in response to chronic inflammation, and several s...

Transforming growth factor-β (TGF-β) mediates growth-inhibitory effects on most target cells via activation of the canonical SMAD signaling pathway. This growth-inhibitory activity may be coupled with cellular differentiation. Our studies demonstrate that TGF-β1 inhibits proliferation of primary, non-transformed human lung fibroblasts in association with the induction of myofibroblast different...

Phyllodes tumors of breast, even histologically diagnosed as benign, can recur locally and have metastatic potential. Histologic markers only have limited value in predicting the clinical behavior of phyllodes tumors. It remains unknown what drives the malignant progression of phyllodes tumors. We found that the expression of myofibroblast markers, a-smooth muscle actin (a-SMA), fibroblast acti...

The incidence of heart failure with concomitant cardiac fibrosis is very high in developed countries. Fibroblast activation in heart is causal to cardiac fibrosis as they convert to hypersynthetic cardiac myofibroblasts. There is no known treatment for cardiac fibrosis. Myofibroblasts contribute to the inappropriate remodeling of the myocardial interstitium, which leads to reduced cardiac funct...

Numerous studies support the idea that the myofibroblast is a key cell responsible for the tissue contraction in Dupuytren's disease. In vitro models have been developed to study the underlying cellular basis of myofibroblast differentiation and contraction. Studies suggest that the growth factor TGF-beta 1 combined with mechanical stress can promote the differentiation of fibroblasts into myof...

Phyllodes tumors of breast, even histologically diagnosed as benign, can recur locally and have metastatic potential. Histologic markers only have limited value in predicting the clinical behavior of phyllodes tumors. It remains unknown what drives the malignant progression of phyllodes tumors. We found that the expression of myofibroblast markers, α-smooth muscle actin (α-SMA), fibroblast acti...

OBJECTIVE High circulating free fatty acids, commonly associated with obesity and insulin resistance, impair structure and function of the microvasculature. However, the mechanisms by which fatty acids cause microvascular remodeling are unclear. Using the mesangial cell model of microvascular pericytes, we demonstrate that the monounsaturated free fatty acid oleate induces a myofibroblast pheno...