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The human ortholog of rodent FIZZ1 has not been identified, but human FIZZ2 has significant sequence homology to both rodent FIZZ2 (59%) and FIZZ1 (50%). Given the greater homology to rodent FIZZ2, analyzing the role of FIZZ2 in a rodent model of bleomycin-induced pulmonary fibrosis would be of greater potential relevance to human fibrotic lung disease. The results showed that FIZZ2 was highly induced in lungs of rodents with bleomycin-induced pulmonary fibrosis and of human patients with idiopathic pulmonary fibrosis. FIZZ2 expression was induced in rodent and human lung epithelial cells by Th2 cytokines, which was mediated via STAT6 signaling. The FIZZ2 induction in murine lungs was found to be essential for pulmonary fibrosis, as FIZZ2 deficiency significantly suppressed pulmonary fibrosis and associated enhanced extracellular matrix and cytokine gene expression. In vitro analysis indicated that FIZZ2 could stimulate type I collagen and \u03b1-smooth muscle actin expression in lung fibroblasts. Furthermore, FIZZ2 was shown to have chemoattractant activity for bone marrow (BM) cells, especially BM-derived CD11c+ dendritic cells. Notably, lung recruitment of BM-derived cells was impaired in FIZZ2 knockout mice. These findings suggest that FIZZ2 is a Th2-associated multifunctional mediator with potentially important roles in the pathogenesis of fibrotic lung diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1000964","type":"journal-article","created":{"date-parts":[[2011,5,21]],"date-time":"2011-05-21T03:16:18Z","timestamp":1305947778000},"page":"450-461","source":"Crossref","is-referenced-by-count":65,"title":["FIZZ2\/RELM-\u03b2 Induction and Role in Pulmonary Fibrosis"],"prefix":"10.1093","volume":"187","author":[{"given":"Tianju","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Michigan Medical School , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Ah","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Pathology, Chonbuk National University Medical School , Jeonju 561-180 ,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfeng","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan Medical School , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology, Chonbuk National University Medical School , Jeonju 561-180 ,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung-Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Chonbuk National University Medical School , Jeonju 561-180 ,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Ullenbruch","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan Medical School , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan Medical School , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan Medical School , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon Young","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan Medical School , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary D","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myoung Ja","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Pathology, Chonbuk National University Medical School , Jeonju 561-180 ,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sem H","family":"Phan","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan Medical School , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,7,1]]},"reference":[{"key":"2025032410194217600_r1","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1056\/NEJMra003200","article-title":"Idiopathic pulmonary fibrosis","volume":"345","author":"Gross","year":"2001","journal-title":"N. 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