Club cell secretory protein deficiency leads to altered lung function

Jing Zhai, Michael Insel, Kenneth J. Addison, Debra A. Stern, William Pederson, Alane Dy, Joselyn Rojas-Quintero, Caroline A. Owen, Duane L Sherrill, Wayne J Morgan, Anne L Wright, Marilyn Halonen, Fernando Martinez, Monica Kraft, Stefano Guerra, Julie G. Ledford

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Rationale: CC16 (club cell secretory protein-16), a member of the secretoglobin family, is one of the most abundant proteins in normal airway secretions and has been described as a serum biomarker for obstructive lung diseases. Objectives: To determine whether low CC16 is a marker for airway pathology or is implicated in the pathophysiology of progressive airway damage in these conditions. Methods: Using human data from the birth cohort of the Tucson Children’s Respiratory Study, we examined the relation of circulating CC16 levels with pulmonary function and responses to bronchial methacholine challenge from childhood up to age 32 years. In wild-type and CC162/2 mice, we set out to comprehensively examine pulmonary physiology, inflammation, and remodeling in the naive airway. Measurements and Main Results: We observed that Tucson Children’s Respiratory Study participants in the lowest tertile of serum CC16 had significant deficits in their lung function and enhanced airway hyperresponsiveness to methacholine challenge from 11 years throughout young adult life. Similarly, CC162/2 mice had significant deficits in lung function and enhanced airway hyperresponsiveness to methacholine as compared with wild-type mice, which were independent of inflammation and mucin production. As compared with wild-type mice, CC162/2 mice had significantly elevated gene expression of procollagen type I, procollagen type III, and a-smooth muscle actin, areas of pronounced collagen deposition and significantly enhanced smooth muscle thickness. Conclusions: Our findings support clinical observations by providing evidence that lack of CC16 in the lung results in dramatically altered pulmonary function and structural alterations consistent with enhanced remodeling.

Original languageEnglish (US)
Pages (from-to)302-312
Number of pages11
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume199
Issue number3
DOIs
StatePublished - Feb 1 2019

Fingerprint

Protein Deficiency
Methacholine Chloride
Lung
Secretoglobins
Smooth Muscle
Obstructive Lung Diseases
Collagen Type III
Mucins
Collagen Type I
Serum
Actins
Young Adult
Pneumonia
Proteins
Collagen
Biomarkers
Parturition
Pathology
Inflammation
Gene Expression

Keywords

  • Asthma
  • CC16
  • CCSP
  • COPD
  • Uteroglobin

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Zhai, J., Insel, M., Addison, K. J., Stern, D. A., Pederson, W., Dy, A., ... Ledford, J. G. (2019). Club cell secretory protein deficiency leads to altered lung function. American Journal of Respiratory and Critical Care Medicine, 199(3), 302-312. https://doi.org/10.1164/rccm.201807-1345OC

Club cell secretory protein deficiency leads to altered lung function. / Zhai, Jing; Insel, Michael; Addison, Kenneth J.; Stern, Debra A.; Pederson, William; Dy, Alane; Rojas-Quintero, Joselyn; Owen, Caroline A.; Sherrill, Duane L; Morgan, Wayne J; Wright, Anne L; Halonen, Marilyn; Martinez, Fernando; Kraft, Monica; Guerra, Stefano; Ledford, Julie G.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 199, No. 3, 01.02.2019, p. 302-312.

Research output: Contribution to journalArticle

Zhai, J, Insel, M, Addison, KJ, Stern, DA, Pederson, W, Dy, A, Rojas-Quintero, J, Owen, CA, Sherrill, DL, Morgan, WJ, Wright, AL, Halonen, M, Martinez, F, Kraft, M, Guerra, S & Ledford, JG 2019, 'Club cell secretory protein deficiency leads to altered lung function', American Journal of Respiratory and Critical Care Medicine, vol. 199, no. 3, pp. 302-312. https://doi.org/10.1164/rccm.201807-1345OC
Zhai, Jing ; Insel, Michael ; Addison, Kenneth J. ; Stern, Debra A. ; Pederson, William ; Dy, Alane ; Rojas-Quintero, Joselyn ; Owen, Caroline A. ; Sherrill, Duane L ; Morgan, Wayne J ; Wright, Anne L ; Halonen, Marilyn ; Martinez, Fernando ; Kraft, Monica ; Guerra, Stefano ; Ledford, Julie G. / Club cell secretory protein deficiency leads to altered lung function. In: American Journal of Respiratory and Critical Care Medicine. 2019 ; Vol. 199, No. 3. pp. 302-312.
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abstract = "Rationale: CC16 (club cell secretory protein-16), a member of the secretoglobin family, is one of the most abundant proteins in normal airway secretions and has been described as a serum biomarker for obstructive lung diseases. Objectives: To determine whether low CC16 is a marker for airway pathology or is implicated in the pathophysiology of progressive airway damage in these conditions. Methods: Using human data from the birth cohort of the Tucson Children’s Respiratory Study, we examined the relation of circulating CC16 levels with pulmonary function and responses to bronchial methacholine challenge from childhood up to age 32 years. In wild-type and CC162/2 mice, we set out to comprehensively examine pulmonary physiology, inflammation, and remodeling in the naive airway. Measurements and Main Results: We observed that Tucson Children’s Respiratory Study participants in the lowest tertile of serum CC16 had significant deficits in their lung function and enhanced airway hyperresponsiveness to methacholine challenge from 11 years throughout young adult life. Similarly, CC162/2 mice had significant deficits in lung function and enhanced airway hyperresponsiveness to methacholine as compared with wild-type mice, which were independent of inflammation and mucin production. As compared with wild-type mice, CC162/2 mice had significantly elevated gene expression of procollagen type I, procollagen type III, and a-smooth muscle actin, areas of pronounced collagen deposition and significantly enhanced smooth muscle thickness. Conclusions: Our findings support clinical observations by providing evidence that lack of CC16 in the lung results in dramatically altered pulmonary function and structural alterations consistent with enhanced remodeling.",
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N2 - Rationale: CC16 (club cell secretory protein-16), a member of the secretoglobin family, is one of the most abundant proteins in normal airway secretions and has been described as a serum biomarker for obstructive lung diseases. Objectives: To determine whether low CC16 is a marker for airway pathology or is implicated in the pathophysiology of progressive airway damage in these conditions. Methods: Using human data from the birth cohort of the Tucson Children’s Respiratory Study, we examined the relation of circulating CC16 levels with pulmonary function and responses to bronchial methacholine challenge from childhood up to age 32 years. In wild-type and CC162/2 mice, we set out to comprehensively examine pulmonary physiology, inflammation, and remodeling in the naive airway. Measurements and Main Results: We observed that Tucson Children’s Respiratory Study participants in the lowest tertile of serum CC16 had significant deficits in their lung function and enhanced airway hyperresponsiveness to methacholine challenge from 11 years throughout young adult life. Similarly, CC162/2 mice had significant deficits in lung function and enhanced airway hyperresponsiveness to methacholine as compared with wild-type mice, which were independent of inflammation and mucin production. As compared with wild-type mice, CC162/2 mice had significantly elevated gene expression of procollagen type I, procollagen type III, and a-smooth muscle actin, areas of pronounced collagen deposition and significantly enhanced smooth muscle thickness. Conclusions: Our findings support clinical observations by providing evidence that lack of CC16 in the lung results in dramatically altered pulmonary function and structural alterations consistent with enhanced remodeling.

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