Familial idiopathic pulmonary fibrosis in a young female

Sritharan, Sajitha Sophia; Gajewska, Marta; Skytte, Anne‐Bine; Madsen, Line Bille; Bendstrup, Elisabeth

doi:10.1016/j.rmcr.2018.03.005

Cited by 5 publications

(9 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present study describes for the first time a large number of functionally assessed pathogenic SFTPA1 and SFTPA2 mutations in 14 independent families. Three mutations were identified in SFTPA1 and eight in SFTPA2, bringing the total number of reported SFTPA1 and SFTPA2 mutations to five and 14 respectively (supplementary table S2) [11,[14][15][16][17][18][19]. Interestingly, all the described mutations are located in exon 6 that encodes the protein CRD and all but one ( p.Tyr208His) were found in the heterozygous state.…”

Section: Discussionmentioning

confidence: 99%

“…17 Pulmonology Dept, Larrey Hospital, Toulouse, France. 18 Pulmonology Dept, Pasteur Hospital, Nice, France. 19 Pathology Dept, Foch Hospital, Suresnes, France.…”

Section: Patientsmentioning

confidence: 99%

“…Indeed, over the last few years, only 11 SFTPA1 or SFTPA2 mutations have been reported in patients with familial forms of ILD and lung cancer. The pathogenicity of these mutations was attested by functional tests for only five of them [11,[14][15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Functional assessment and phenotypic heterogeneity of SFTPA1 and SFTPA2 mutations in interstitial lung diseases and lung cancer

et al. 2020

View full text Add to dashboard Cite

IntroductionInterstitial lung diseases (ILD) can be caused by mutations in the SFTPA1 and SFTPA2 genes, which encode the surfactant protein complex (SP)-A. Only 11 SFTPA1/2 mutations have so far been reported worldwide, of which 5 have been functionally assessed. In the framework of ILD molecular diagnosis, we identified 14 independent patients with pathogenic SFTPA1 or SFTPA2 mutations. The present study aimed to functionally assess the 11 different mutations identified and to accurately describe the disease phenotype of the patients and their affected relatives.MethodsThe consequences of the 11 SFTPA1/2 mutations were analysed both in vitro by studying the production and secretion of the corresponding mutated proteins and ex vivo by analysing SP-A expression on lung tissue samples. The associated disease phenotypes were documented.ResultsFor the 11 identified mutations, protein production was preserved, but secretion was abolished. The expression pattern of lung SP-A, available in 6 patients, was altered. The family history reported ILD and/or lung adenocarcinoma in 13/14 (93%) families. Among the 28 SFTPA1/2 mutation carriers, the mean age at ILD onset was 45 [0.6–65] years and 48% of them underwent lung transplantation (mean age 51); 7 carriers were asymptomatic.DiscussionThis study, which expands the molecular and clinical spectrum of SP-A disorders, shows that those pathogenic SFTPA1/A2 mutations share similar consequences on SP-A secretion in cell models and lung tissue immunostaining, whereas they are associated with a highly variable phenotypic expression of the disease, ranging from severe forms requiring lung transplantation to incomplete penetrance.

show abstract

Section: Discussionmentioning

confidence: 99%

“…17 Pulmonology Dept, Larrey Hospital, Toulouse, France. 18 Pulmonology Dept, Pasteur Hospital, Nice, France. 19 Pathology Dept, Foch Hospital, Suresnes, France.…”

Section: Patientsmentioning

confidence: 99%

See 1 more Smart Citation

Functional assessment and phenotypic heterogeneity of SFTPA1 and SFTPA2 mutations in interstitial lung diseases and lung cancer

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In addition, as the surfactant-producing cells of the alveoli, AT2 cells secrete surfactant to maintain surface tension and alveolar patency. Mutations in these surfactants are associated with pathogenesis in some familial and sporadic forms of IPF in humans and IPF animal models [59][60][61][62]. Therefore, organoid cultures of AT2 cells and/or other alveolar stem/progenitor cells from IPF patients can be used to test the reparative and/or secretory function of these stem/progenitor cells.…”

Section: Organoid Modeling Of Idiopathic Pulmonary Fibrosismentioning

confidence: 99%

Organoids as a Powerful Model for Respiratory Diseases

Liu

Wu²,

Sun³

et al. 2020

Stem Cells International

View full text Add to dashboard Cite

Insults to the alveoli usually lead to inefficient gas exchange or even respiratory failure, which is difficult to model in animal studies. Over the past decade, stem cell-derived self-organizing three-dimensional organoids have emerged as a new avenue to recapitulate respiratory diseases in a dish. Alveolar organoids have improved our understanding of the mechanisms underlying tissue homeostasis and pathological alterations in alveoli. From this perspective, we review the state-of-the-art technology on establishing alveolar organoids from endogenous lung epithelial stem/progenitor cells or pluripotent stem cells, as well as the use of alveolar organoids for the study of respiratory diseases, including idiopathic pulmonary fibrosis, tuberculosis infection, and respiratory virus infection. We also discuss challenges that need to be overcome for future application of alveolar organoids in individualized medicine.

show abstract

“…7,8 There are ample causes for the occurrence of IPF, but the unknown nature of the molecular cause gives it the name "Idiopathic." 9 IPF should be expelled from the category of pulmonary disorders and rather be classified among connective tissue diseases. 10 The primary target during IPF is damage to the alveolar epithelial cells (AECs).…”

mentioning

confidence: 99%

Targeting anti‐aging protein sirtuin (Sirt) in the diagnosis of idiopathic pulmonary fibrosis

Shaikh

Prabhu

Bhandary

2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) is a severe, incurable, age‐associated respiratory disorder that has gained significance because of its unknown etiology and lack of therapeutic approaches. IPF causes maximum damage to the alveolar epithelial cells, thereby leading to lung remodeling and initiating epithelial to mesenchymal transition (EMT). The actual molecular mechanisms underlying IPF still remain unclear, and knowledge about these mechanisms would be helpful in its diagnosis. Sirtuins (Sirt) are class of NAD+‐dependent proteins, widely known to exert positive and protective effects on age‐related diseases such as diabetes, cancer, and so on, and are also involved in regulating IPF. The sirtuin family comprises of seven members (Sirt1 to Sirt7), out of which Sirt1, Sirt3, Sirt6, and Sirt7 exert positive effects on IPF. Sirt1 is associated with aging and inhibits cellular senescence and fibrosis. Sirt1 is well recognized in controlling pulmonary fibrosis and is also considered as a prime positive mediator of EMT. The expressions of Sirt3 protein tend to decline in IPF patients; hence it is known as an anti‐fibrotic protein. Sirt6 indeed has been proven to reduce EMT during IPF. Decreased levels of Sirt7 during IPF regulate lung fibroblasts. Hence, active levels of Sirt1, Sirt3, Sirt6, and Sirt7 can be attractive target models to elucidate a novel potential therapeutic approach for IPF. In this prospect, we have discussed the role of Sirtuins in pulmonary fibrosis by exploring the recent research evidence that highlight the role of sirtuins and also describes their protective effects.

show abstract

Familial idiopathic pulmonary fibrosis in a young female

Cited by 5 publications

References 7 publications

Functional assessment and phenotypic heterogeneity of SFTPA1 and SFTPA2 mutations in interstitial lung diseases and lung cancer

Functional assessment and phenotypic heterogeneity of SFTPA1 and SFTPA2 mutations in interstitial lung diseases and lung cancer

Organoids as a Powerful Model for Respiratory Diseases

Targeting anti‐aging protein sirtuin (Sirt) in the diagnosis of idiopathic pulmonary fibrosis

Contact Info

Product

Resources

About