The Role of Pathological Aging in Cardiac and Pulmonary Fibrosis.

Aging promotes a range of degenerative pathologies characterized by progressive losses of tissue and/or cellular function. Fibrosis is the hardening, overgrowth and scarring of various tissues characterized by the accumulation of extracellular matrix components. Aging is an important predisposing factor common for fibrotic heart and respiratory disease.

Casein Kinase 1δ/ε Inhibitor, PF670462 Attenuates the Fibrogenic Effects of Transforming Growth Factor-β in Pulmonary Fibrosis.

Transforming growth factor-beta (TGF-β) is a major mediator of fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). However, therapeutic global inhibition of TGF-β is limited by unwanted immunosuppression and mitral valve defects. We performed an extensive literature search to uncover a little-known connection between TGF-β signaling and casein kinase (CK) activity.

The Processes and Mechanisms of Cardiac and Pulmonary Fibrosis.

Fibrosis is the formation of fibrous connective tissue in response to injury. It is characterized by the accumulation of extracellular matrix components, particularly collagen, at the site of injury. Fibrosis is an adaptive response that is a vital component of wound healing and tissue repair.

Pro-inflammatory mediators increase levels of the noncoding RNA GAS5 in airway smooth muscle and epithelial cells.

The long noncoding RNA (lncRNA) GAS5 has been found to act as a decoy for the glucocorticoid receptor (GR), thus implicating GAS5 as a potential regulator of glucocorticoid sensitivity and resistance. Airway smooth muscle (ASM) cells and airway epithelial cells (AEC) play an important role in the pathogenesis and persistence of asthma and other chronic airways diseases. These airway structural cell types are also important cellular targets of the anti-inflammatory actions of glucocorticoids.

Fibrillar collagen clamps lung mesenchymal cells in a nonproliferative and noncontractile phenotype.

Pulmonary fibrosis is characterized by phenotypic changes to mesenchymal cells and an increase in the deposition of fibrillar collagen (fCollagen). This study investigated the effect of type I fCollagen on the phenotypic plasticity of human parenchymal fibroblasts (PFbs) in vitro. Cell numbers were 45% lower when cultured on fCollagen as compared with culture on its degradation product, monomeric collagen (mCollagen).

Resistance of fibrogenic responses to glucocorticoid and 2-methoxyestradiol in bleomycin-induced lung fibrosis in mice.

Bleomycin-induced lung fibrosis in mice reproduces some key features of pulmonary fibrosis in humans including alveolar inflammation, myofibroblast proliferation, and collagen deposition. Glucocorticoids have been used as first-line therapy for the treatment of lung fibrosis, although their clinical efficacy is equivocal. We examined the effect of the glucocorticoid, methylprednisolone (MP), and the estrogen metabolite, 2-methoxyestradiol (2MEO) on bleomycin-induced bronchoalveolar inflammation, fibrosis, and changes in lung function.