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To this aim, we compared molecular and biophysical characteristics of fibroblasts concurrently isolated from normal human proximal bronchi (B-FBR) and distal lung parenchyma (P-FBR). Using quantitative RT-PCR, spontaneous expression of more than 30 genes related to repair and remodeling was analyzed. All P-FBR lines demonstrated significantly increased basal \u03b1\u2013smooth muscle actin (\u03b1-SMA) mRNA and protein expression levels when compared with donor-matched B-FBR. These differences were not associated with sex, age, or disease history of lung tissue donors. In contrast to B-FBR, P-FBR displayed enhanced transforming growth factor (TGF)-\u03b2\/Smad signaling at baseline, and inhibition of either ALK-5 or neutralization of endogenously produced and activated TGF-\u03b2 substantially decreased basal \u03b1-SMA protein in P-FBR. Both B-FBR and P-FBR up-regulated \u03b1-SMA after stimulation with TGF-\u03b21, and basal expression levels of TGF-\u03b21, TGF-\u03b2RI, and TGF-\u03b2RII were not significantly different between fibroblast pairs. Blockade of metalloproteinase-dependent activation of endogenous TGF-\u03b2 did not significantly modify \u03b1-SMA expression in P-FBR. However, resistance to mechanical tension of these cells was significantly higher in comparison with B-FBR, and added TGF-\u03b21 significantly increased stiffness of both cell monolayers. Our data suggest that in contrast with human normal bronchial tissue explants, lung parenchyma produces mesenchymal cells with a myofibroblastic phenotype by intrinsic mechanisms of TGF-\u03b2 activation in feed-forward manner. These results also offer a new insight into mechanisms of human fibroblast heterogeneity and their function in the airway and lung tissue repair and remodeling.<\/jats:p>","DOI":"10.1165\/rcmb.2009-0318oc","type":"journal-article","created":{"date-parts":[[2010,1,8]],"date-time":"2010-01-08T22:04:36Z","timestamp":1262988276000},"page":"641-651","source":"Crossref","is-referenced-by-count":59,"title":["Human Lung Parenchyma but Not Proximal Bronchi Produces Fibroblasts with Enhanced TGF-\u03b2 Signaling and \u03b1-SMA Expression"],"prefix":"10.1093","volume":"43","author":[{"given":"Dmitri V.","family":"Pechkovsky","sequence":"first","affiliation":[{"name":"UBC James Hogg Research Centre, Heart + Lung Institute"},{"name":"Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tillie 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