Clara Cells and Clara Cell 10 kD Protein (CC10)

Singh, Gurmukh; Katyal, Sikandar L.

doi:10.1165/ajrcmb.17.2.f138

Cited by 155 publications

(128 citation statements)

References 9 publications

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“…Goblet cells are glandular columnar cells more localized in bronchi that secrete mucin; MUC5A/C is the gene that encodes Mucin 5AC and is associated with goblet cells in the respiratory epithelium (48). Clara cells are nonciliated secretory epithelial cells lining the pulmonary airways that secrete Clara cell secretory protein (CCSP) (also known as CC10, CC16, or uteroglobin) (49). Clara cells were identified during differentiation from iPSCs by the expression of CC10 in vesicle-like structures on the apical surface of the epithelial layer (representative images are shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Generation of multiciliated cells in functional airway epithelia from human induced pluripotent stem cells

Firth

Dargitz

Qualls

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

221

214

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Despite a significant improvement in the availability of therapeutic options to treat lung diseases, pulmonary disease still remains a major cause of morbidity and mortality around the world. Currently there are limited opportunities to study human lung disease either in vivo and in vitro. Using induced pluripotent stem cells (iPSC) we have generated a reproducible differentiation protocol to make mature post‐mitotic multiciliated cells in a functional airway epithelium. iPSC were generated from human skin biopsies and differentiated via FOXA2+SOX17+ definitive endoderm (>90% efficiency) to FOXA2+NKx2.1+ anterior foregut endoderm, FOXA2+NKx2.1+SOX2+ (~50% efficiency) pulmonary endoderm and then matured in an air liquid interface. Robust multiciliogenesis occurred when Notch signaling was inhibited and was confirmed by; i) the assembly of multiple pericentrin stained centrioles at the apical surface, ii) expression of transcription factor FOXJ1 and iii) presence of multiple acetylated tubulin labeled cilia projections in individual cells. The presence of NKx2.1+CC10+ Clara cells, MUC5A/C+ goblet cells and FOXA2+p63+ basal cells was also confirmed showing we are generating a complete polarized epithelial cell layer comprised of all relevant cell types. Functional cAMP activated and CFTRinh‐172 sensitive CFTR currents were recorded in isolated epithelial cells by whole cell patch clamp technique. Furthermore, we have corrected the deltaF508 mutation in the CFTR gene (>80% of all cases of CF) using a combination of CRISPR‐Cas9 endonuclease‐mediated genome editing and piggyBac transposase technologies, in the CF patient‐derived iPSC. The generation of mature multiciliated cells in a human iPSC differentiated respiratory epithelium and the ability to correct disease causing mutations provides a significant advancement toward modeling a number of human respiratory diseases in vitro. Grant Funding Source: Supported in part by CIRM and the Berger Foundation

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Section: Resultsmentioning

confidence: 99%

Generation of multiciliated cells in functional airway epithelia from human induced pluripotent stem cells

Firth

Dargitz

Qualls

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

221

214

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“…Thus, IL-13 appears to directly stimulate epithelial mucin formation, but the type of target epithelial cells and the cellular process for mucous cell differentiation remain less certain. Also a transition of Clara to goblet cells in human disease is reported [32].…”

Section: Goblet Cell Metaplasia From Clara and Ciliated Cellsmentioning

confidence: 99%

Molecular Mechanisms of Metaplasia, Differentiation and Hyperplasia of Goblet Cellin Allergic Asthma

Hayashi¹

2012

J Aller Ther

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Bronchial allergic asthma (asthma) is an airway inflammation characterized by airflow obstruction of variable degrees with bronchial hyper-responsiveness and is induced by a complex interaction of environmental and genetic factors. Asthma of the human can be divided into an immediate-and a late-phase reaction, and some of the patients develop a late-phase reaction after a symptom-free interval. Hallmarks of asthma are mucus overproduction by goblet cells associated with responses of helper T(Th)2 cells. Mucus hypersecretion from goblet cells themselves or by metaplasia and/or hyperplasia of goblet cells appears to be associated with disease severity in asthma, because mucus production by those cells in local bronchial-bronchiolar lesions causes airway mucus plugging. However, the mechanisms of mucus production are not fully understood. Molecular mechanisms of goblet cell metaplasia, differentiation and hyperplasia will be reviewed in this article. Also, the relationship between allergic inflammation in Th1/Th2 paradigm shift and thymic stromal lymphopoietin (TSLP) was included for the understanding of goblet cell response in asthma. The clarification of mechanisms of mucin production in vivo may lead to the development of novel therapeutic strategies to suppress mucus production in asthma.

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“…UGRP1 is similar to CC16 with regard to its amino acid sequence and site of tissue-specific expression (4). As demonstrated by in vivo and in vitro studies (6,16), CC16 functions as an anti-inflammatory agent. Similarly, UGRP1 has been suggested to exhibit anti-inflammatory functions.…”

Section: Discussionmentioning

confidence: 93%

“…These genes encode proinflammatory cytokines, such as interleukin-3, −4, −5, −9 and −13 (5). As a result of the similarity in the amino acid sequences of UGRP1 and Clara cell protein (CC16), which exhibits several immunomodulatory and anti-inflammatory effects, it is possible that UGRP1 may possess similar functions (6). Furthermore, UGRP1 mRNA is predominantly expressed in the lung, with a high level of expression in the epithelial cells of the lung airway (4).…”

Section: Introductionmentioning

confidence: 99%

Association between the -112G/A polymorphism of uteroglobulin-related protein 1 gene and asthma risk: A meta-analysis

Xie

Shen

et al. 2014

Experimental and Therapeutic Medicine

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The aim of this study was to investigate the correlation between the -112G/A polymorphism of the uteroglobulin-related protein 1 (UGRP1) gene and asthma risk using meta-analysis. PubMed, BIOSIS Previews and EBSCOhost were searched, and data were extracted independently by two reviewers. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to assess the strength of the associations. Statistical analysis was performed using Review Manager 5.2 and STATA 11.0 software. Six studies, involving 816 cases and 1,165 controls, were included in the analysis. The meta-analysis showed a significant correlation between the UGRP1-112G/A polymorphism and asthma for AA versus GG (P=0.01) and AA versus GA/GG (P=0.02). Furthermore, stratification by ethnicity revealed a significant correlation between the -112G/A polymorphism and asthma for A versus G (P=0.02), AA versus GG (P=0.01) and AA versus GA/GG (P=0.03) in Asians, but not in Caucasians. When stratified by atopy, a significant correlation was observed for A versus G (P=0.02) and AA/GA versus GG (P=0.04) in the mixed group. No correlation was observed for age stratification. Results of the current meta-analysis indicate that the -112G/A polymorphism of the UGRP1 gene is likely to contribute to asthma risk, particularly in the Asian population.

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Clara Cells and Clara Cell 10 kD Protein (CC10)

Cited by 155 publications

References 9 publications

Generation of multiciliated cells in functional airway epithelia from human induced pluripotent stem cells

Generation of multiciliated cells in functional airway epithelia from human induced pluripotent stem cells

Molecular Mechanisms of Metaplasia, Differentiation and Hyperplasia of Goblet Cellin Allergic Asthma

Association between the -112G/A polymorphism of uteroglobulin-related protein 1 gene and asthma risk: A meta-analysis

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