Beyond TGFβ – Novel ways to target airway and parenchymal fibrosis

Boorsma, Carian E.; Dekkers, Bart G. J.; Dijk, Eline M van; Kumawat, Kuldeep; Richardson, J.; Burgess, Janette K.; John, Alison E.

doi:10.1016/j.pupt.2014.08.009

Cited by 15 publications

(13 citation statements)

References 258 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, IPF can be defined as an age-related disease. Neither mechanisms of IPF, nor effective pharmacological therapies have been established to date [ 4 , 11 , and 12 ]. The only effective treatment currently available for progressive lung fibrosis is lung transplantation [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Cellular senescence-like features of lung fibroblasts derived from idiopathic pulmonary fibrosis patients

Yanai

Shteinberg

Porat

et al. 2015

Aging

154

100

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) is an age-related fatal disease with unknown etiology and no effective treatment. In this study, we show that primary cultures of fibroblasts derived from lung biopsies of IPF patients exhibited (i) accelerated replicative cellular senescence (CS); (ii) high resistance to oxidative-stress-induced cytotoxicity or CS; (iii) a CS-like morphology (even at the proliferative phase); and (iv) rapid accumulation of senescent cells expressing the myofibroblast marker α-SMA. Our findings suggest that CS could serve as a bridge connecting lung aging and its quite frequent outcome -- pulmonary fibrosis, and be an important player in the disease progression. Consequently, targeting senescent cells offers the potential of being a promising therapeutic approach.

show abstract

Section: Introductionmentioning

confidence: 99%

Cellular senescence-like features of lung fibroblasts derived from idiopathic pulmonary fibrosis patients

Yanai

Shteinberg

Porat

et al. 2015

Aging

154

100

View full text Add to dashboard Cite

show abstract

“…Fibrosis is also a characteristic of many respiratory diseases that differ markedly in etiology, phenotype, and symptoms. Fibrosis can occur in the airway wall, as in the larger airways in asthma (Boorsma et al, 2014 ) and around the small airways in chronic obstructive pulmonary disease (Jones et al, 2016 ), or the lung parenchyma, as in idiopathic pulmonary fibrosis (IPF) and acute respiratory distress syndrome (ARDS). The fibrosis in IPF is particularly prominent, causing irreversible lung scarring and respiratory failure (Boorsma et al, 2014 ; Burnham et al, 2014 ; Wuyts et al, 2014 ).…”

Section: Fibrotic Disease Of the Lungsmentioning

confidence: 99%

The Processes and Mechanisms of Cardiac and Pulmonary Fibrosis

et al. 2017

View full text Add to dashboard Cite

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. However, its continued activation is highly detrimental and a common final pathway of numerous disease states including cardiovascular and respiratory disease. Worldwide, fibrotic diseases cause over 800,000 deaths per year, accounting for ~45% of total deaths. With an aging population, the incidence of fibrotic disease and subsequently the number of fibrosis-related deaths will rise further. Although, fibrosis is a well-recognized cause of morbidity and mortality in a range of disease states, there are currently no viable therapies to reverse the effects of chronic fibrosis. Numerous predisposing factors contribute to the development of fibrosis. Biological aging in particular, interferes with repair of damaged tissue, accelerating the transition to pathological remodeling, rather than a process of resolution and regeneration. When fibrosis progresses in an uncontrolled manner, it results in the irreversible stiffening of the affected tissue, which can lead to organ malfunction and death. Further investigation into the mechanisms of fibrosis is necessary to elucidate novel, much needed, therapeutic targets. Fibrosis of the heart and lung make up a significant proportion of fibrosis-related deaths. It has long been established that the heart and lung are functionally and geographically linked when it comes to health and disease, and thus exploring the processes and mechanisms that contribute to fibrosis of each organ, the focus of this review, may help to highlight potential avenues of therapeutic investigation.

show abstract

“…In fact, eosinophils are a rich source of TGF-β and eosinophil depleted mice are protected from peri-bronchial collagen deposition and increased ASM mass in response to chronic allergen exposure [258]. Recent studies have also uncovered key roles for other TGF-β superfamily members, including activin-A, and bone morphogenic proteins and the epithelial cell-derived cytokines, IL-33, TSLP and IL-25, in airway remodelling in asthma [260][261][262]. Hence, the development of biologics targeting the effects of these cytokines on the control of airway remodelling represents a fruitful avenue for future research that may be translated to better treatment options for asthmatics [261,262].…”

Section: Airway Remodellingmentioning

confidence: 99%

Addressing unmet needs in understanding asthma mechanisms

et al. 2017

View full text Add to dashboard Cite

Asthma is a heterogeneous, complex disease with clinical phenotypes that incorporate persistent symptoms and acute exacerbations. It affects many millions of Europeans throughout their education and working lives and puts a heavy cost on European productivity. There is a wide spectrum of disease severity and control. Therapeutic advances have been slow despite greater understanding of basic mechanisms and the lack of satisfactory preventative and disease modifying management for asthma constitutes a significant unmet clinical need. Preventing, treating and ultimately curing asthma requires co-ordinated research and innovation across Europe. The European Asthma Research and Innovation Partnership (EARIP) is an FP7-funded programme which has taken a co-ordinated and integrated approach to analysing the future of asthma research and development. This report aims to identify the mechanistic areas in which investment is required to bring about significant improvements in asthma outcomes.

show abstract

Beyond TGFβ – Novel ways to target airway and parenchymal fibrosis

Cited by 15 publications

References 258 publications

Cellular senescence-like features of lung fibroblasts derived from idiopathic pulmonary fibrosis patients

Cellular senescence-like features of lung fibroblasts derived from idiopathic pulmonary fibrosis patients

The Processes and Mechanisms of Cardiac and Pulmonary Fibrosis

Addressing unmet needs in understanding asthma mechanisms

Contact Info

Product

Resources

About