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Hhip haploinsufficiency sensitizes mice to age-related emphysema.
Lao, Taotao; Jiang, Zhiqiang; Yun, Jeong; Qiu, Weiliang; Guo, Feng; Huang, Chunfang; Mancini, John Dominic; Gupta, Kushagra; Laucho-Contreras, Maria E; Naing, Zun Zar Chi; Zhang, Li; Perrella, Mark A; Owen, Caroline A; Silverman, Edwin K; Zhou, Xiaobo.
Affiliation
  • Lao T; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
  • Jiang Z; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
  • Yun J; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
  • Qiu W; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
  • Guo F; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
  • Huang C; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
  • Mancini JD; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
  • Gupta K; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
  • Laucho-Contreras ME; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; Chronic Obstructive Pulmonary Disease Program, The Lovelace Respiratory Research Institute, Albuquerque, NM 87108;
  • Naing ZZ; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
  • Zhang L; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
  • Perrella MA; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; Pediatric Newborn Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115.
  • Owen CA; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; Chronic Obstructive Pulmonary Disease Program, The Lovelace Respiratory Research Institute, Albuquerque, NM 87108;
  • Silverman EK; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
  • Zhou X; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; xiaobo.zhou@channing.harvard.edu.
Proc Natl Acad Sci U S A ; 113(32): E4681-7, 2016 08 09.
Article in En | MEDLINE | ID: mdl-27444019
ABSTRACT
Genetic variants in Hedgehog interacting protein (HHIP) have consistently been associated with the susceptibility to develop chronic obstructive pulmonary disease and pulmonary function levels, including the forced expiratory volume in 1 s (FEV1), in general population samples by genome-wide association studies. However, in vivo evidence connecting Hhip to age-related FEV1 decline and emphysema development is lacking. Herein, using Hhip heterozygous mice (Hhip(+/-)), we observed increased lung compliance and spontaneous emphysema in Hhip(+/-) mice starting at 10 mo of age. This increase was preceded by increases in oxidative stress levels in the lungs of Hhip(+/-) vs. Hhip(+/+) mice. To our knowledge, these results provide the first line of evidence that HHIP is involved in maintaining normal lung function and alveolar structures. Interestingly, antioxidant N-acetyl cysteine treatment in mice starting at age of 5 mo improved lung function and prevented emphysema development in Hhip(+/-) mice, suggesting that N-acetyl cysteine treatment limits the progression of age-related emphysema in Hhip(+/-) mice. Therefore, reduced lung function and age-related spontaneous emphysema development in Hhip(+/-) mice may be caused by increased oxidative stress levels in murine lungs as a result of haploinsufficiency of Hhip.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Membrane Glycoproteins / Carrier Proteins / Emphysema / Haploinsufficiency Limits: Animals Language: En Journal: Proc Natl Acad Sci U S A Year: 2016 Type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Membrane Glycoproteins / Carrier Proteins / Emphysema / Haploinsufficiency Limits: Animals Language: En Journal: Proc Natl Acad Sci U S A Year: 2016 Type: Article