| First Author | Sivaprasad U | Year | 2011 |
| Journal | J Allergy Clin Immunol | Volume | 127 |
| Issue | 1 | Pages | 254-61, 261.e1-6 |
| PubMed ID | 21126757 | Mgi Jnum | J:189949 |
| Mgi Id | MGI:5447387 | Doi | 10.1016/j.jaci.2010.10.009 |
| Citation | Sivaprasad U, et al. (2011) A nonredundant role for mouse Serpinb3a in the induction of mucus production in asthma. J Allergy Clin Immunol 127(1):254-61, 261.e1-6 |
| abstractText | BACKGROUND: Asthma is a major public health burden worldwide. Studies from our group and others have demonstrated that SERPINB3 and SERPINB4 are induced in patients with asthma; however, their mechanistic role in asthma has yet to be determined. OBJECTIVE: To evaluate the role of Serpin3a, the murine homolog of SERPINB3 and SERPINB4, in asthma. METHODS: We studied wild-type Balb/c and Serpinb3a-null mice in house dust mite or IL-13-induced asthma models and evaluated airway hyperresponsiveness, inflammation, and goblet cell hyperplasia. RESULTS: Airway hyperresponsiveness and goblet cell hyperplasia were markedly attenuated in the Serpinb3a-null mice compared with the wild-type mice after allergen challenge, with minimal effects on inflammation. Expression of sterile alpha motif pointed domain containing v-ets avian erythroblastosis virus E26 oncogene homolog transcription factor (SPDEF), a transcription factor that mediates goblet cell hyperplasia, was decreased in the absence of Serpinb3a. IL-13-treated Serpinb3a-null mice showed attenuated airway hyperresponsiveness, inflammation, and mucus production. CONCLUSION: Excessive mucus production and mucus plugging are key pathologic features of asthma, yet the mechanisms responsible for mucus production are not well understood. Our data reveal a novel nonredundant role for Serpinb3a in mediating mucus production through regulation of SPDEF expression. This pathway may be used to target mucus hypersecretion effectively. |
