Processing of Pulmonary Surfactant Protein B by Napsin and Cathepsin H

Ueno, Takayuki; Linder, Stig; Na, Cheng-Lun; Rice, Ward R.; Johansson, Jan; Weaver, Timothy E.

doi:10.1074/jbc.m312029200

Cited by 129 publications

(107 citation statements)

References 45 publications

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“…S7), the Sox9 mutant lung also up-regulated a number of genes, including Sftpb, Sftpc, Lamp3, Napsa, and Ctsh, that are known or were shown (Fig. S12A) to be expressed by differentiated alveolar cells and involved in the production and processing of surfactant proteins (41,42).…”

Section: Negative Correlations Between Branching Morphogenesis and Almentioning

confidence: 99%

Lung epithelial branching program antagonizes alveolar differentiation

Chang¹,

Alanis²,

Miller

et al. 2013

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

171

231

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Mammalian organs, including the lung and kidney, often adopt a branched structure to achieve high efficiency and capacity of their physiological functions. Formation of a functional lung requires two developmental processes: branching morphogenesis, which builds a tree-like tubular network, and alveolar differentiation, which generates specialized epithelial cells for gas exchange. Much progress has been made to understand each of the two processes individually; however, it is not clear whether the two processes are coordinated and how they are deployed at the correct time and location. Here we show that an epithelial branching morphogenesis program antagonizes alveolar differentiation in the mouse lung. We find a negative correlation between branching morphogenesis and alveolar differentiation temporally, spatially, and evolutionarily. Gain-of-function experiments show that hyperactive small GTPase Kras expands the branching program and also suppresses molecular and cellular differentiation of alveolar cells. Loss-of-function experiments show that SRYbox containing gene 9 (Sox9) functions downstream of Fibroblast growth factor (Fgf)/Kras to promote branching and also suppresses premature initiation of alveolar differentiation. We thus propose that lung epithelial progenitors continuously balance between branching morphogenesis and alveolar differentiation, and such a balance is mediated by dual-function regulators, including Kras and Sox9. The resulting temporal delay of differentiation by the branching program may provide new insights to lung immaturity in preterm neonates and the increase in organ complexity during evolution.

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Section: Negative Correlations Between Branching Morphogenesis and Almentioning

confidence: 99%

Lung epithelial branching program antagonizes alveolar differentiation

Chang¹,

Alanis²,

Miller

et al. 2013

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

171

231

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show abstract

“…[1][2][3][4] Napsin A has a role in processing pulmonary surfactant B protein produced by alveolar type II pneumocytes; 5,6 thus, it has been reported to be a good diagnostic marker for the confirmation of primary lung adenocarcinoma together with thyroid transcription factor 1 (TTF-1). [7][8][9][10][11][12][13] Expression of napsin A is also observed in the fetal kidney 14 and proximal tubules of the adult kidney, where it is most likely involved in protein catabolism.…”

mentioning

confidence: 99%

Napsin A is a specific marker for ovarian clear cell adenocarcinoma

et al. 2015

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Ovarian clear cell adenocarcinoma has a relatively poor prognosis among the ovarian cancer subtypes because of its high chemoresistance. Differential diagnosis of clear cell adenocarcinoma from other ovarian surface epithelial tumors is important for its treatment. Napsin A is a known diagnostic marker for lung adenocarcinoma, and expression of napsin A is reported in a certain portion of thyroid and renal carcinomas. However, napsin A expression in ovarian surface epithelial tumors has not previously been examined. In this study, immunohistochemical analysis revealed that in 71 of 86 ovarian clear cell adenocarcinoma patients (83%) and all of the 13 patients with ovarian clear cell adenofibroma, positive napsin A staining was evident. No expression was observed in 30 serous adenocarcinomas, 11 serous adenomas or borderline tumors, 19 endometrioid adenocarcinomas, 22 mucinous adenomas or borderline tumors, 10 mucinous adenocarcinomas, or 3 yolk sac tumors of the ovary. Furthermore, expression of napsin A was not observed in the normal surface epithelium of the ovary, epithelia of the fallopian tubes, squamous epithelium, endocervical epithelium, or the endometrium of the uterus. Therefore, we propose that napsin A is another sensitive and specific marker for distinguishing ovarian clear cell tumors (especially adenocarcinomas) from other ovarian tumors.

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“…Stearoly-CoA desaturase 1 (Scd1) is an enzyme that converts saturated fatty acids into monounsaturated fatty acids and is crucial for the conversion of glycogen into phospholipids in the pulmonary surfactant (Zhang et al, 2004). Napsin (also known as Napsa -Mouse Genome Informatics) is an aspartyl protease known to process SP-B and SP-C into their mature forms (Brasch et al, 2003;Ueno et al, 2004). Remarkably, the expression of Dpp4, Scd1, RBP-L and napsin were all dramatically downregulated in G6-Nkx DH mutants, as measured by Q-PCR and in situ hybridization (Fig.…”

Section: Research Articlementioning

confidence: 99%

GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo

et al. 2007

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In vitro studies have suggested that members of the GATA and Nkx transcription factor families physically interact, and synergistically activate pulmonary epithelial-and cardiac-gene promoters. However, the relevance of this synergy has not been demonstrated in vivo. We show that Gata6-Titf1 (Gata6-Nkx2.1) double heterozygous (G6-Nkx DH) embryos and mice have severe defects in pulmonary epithelial differentiation and distal airway development, as well as reduced phospholipid production. The defects in G6-Nkx DH embryos and mice are similar to those observed in human neonates with respiratory distress syndromes, including bronchopulmonary dysplasia, and differential gene expression analysis reveals essential developmental pathways requiring synergistic regulation by both Gata6 and Titf1 (Nkx2.1). These studies indicate that Gata6 and Nkx2.1 act in a synergistic manner to direct pulmonary epithelial differentiation and development in vivo, providing direct evidence that interactions between these two transcription factor families are crucial for the development of the tissues in which they are co-expressed.

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Processing of Pulmonary Surfactant Protein B by Napsin and Cathepsin H

Abstract: Surfactant protein B (SP-B

Cited by 129 publications

References 45 publications

Lung epithelial branching program antagonizes alveolar differentiation

Lung epithelial branching program antagonizes alveolar differentiation

Napsin A is a specific marker for ovarian clear cell adenocarcinoma

GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo

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