TRANSFORMING GROWTH-FACTOR-BETA REGULATION OF MIGRATION IN WOUNDED RAT INTESTINAL EPITHELIAL MONOLAYERS

被引:230
作者
CIACCI, C
LIND, SE
PODOLSKY, DK
机构
[1] MASSACHUSETTS GEN HOSP, GASTROINTESTINAL UNIT, JACKSON 7, 32 FRUIT ST, BOSTON, MA 02114 USA
[2] BRIGHAM & WOMENS HOSP, DIV HEMATOL & ONCOL, BOSTON, MA 02115 USA
[3] MASSACHUSETTS GEN HOSP, NEW ENGLAND REG PRIMATE RES CTR, BOSTON, MA 02114 USA
关键词
D O I
10.1016/0016-5085(93)90014-4
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: In vitro studies have suggested that transforming growth factor β1 (TGF-β1) plays an important role in the regulation of proliferation of intestinal epithelial cells, effecting strong inhibition of proliferation in intestinal epithelial cell lines. Studies were undertaken to assess its role in repair after injury using an in vitro wounding model. Methods: Wounds were created in confluent monolayers of the intestinal epithelial cell line of IEC-6. Exogenous TGF-β1, conditioned media from wounded IEC-6 cultures, or control media were added. Restitution was quantified as the number of cells migrating across the wound edge. Proliferation was assessed by uptake of bromodeoxyuridine and thymidine incorporation. Results: Although TGF-β was a potent inhibitor of proliferation, it promoted rapid "healing" of the monolayers through stimulation of migration of cells across the wound margin. The physiological importance of this activity was supported by the demonstration that conditioned medium from IEC-6 cells stimulated repair of the wounded monolayers. Effects of the conditioned medium could be entirely blocked by immunoneutralizing anti-TGF-β antisera. Further, addition of protease inhibitors (aprotinin, ε-aminocaproic acid) that prevented the bioactivation of latent TGF-β secreted by the IEC-6 cells also ablated the effect of the conditioned medium. In addition, expression of TGF-β1 messenger RNA was significantly enhanced in the wounded monolayers. Conclusions: These findings suggest that TGF-β may play an important role in reconstitution of epithelial integrity after mucosal injury. © 1993.
引用
收藏
页码:93 / 101
页数:9
相关论文
共 38 条
[11]   TYPE-1 TRANSFORMING GROWTH-FACTOR-BETA - AMPLIFIED EXPRESSION AND SECRETION OF MATURE AND PRECURSOR POLYPEPTIDES IN CHINESE-HAMSTER OVARY CELLS [J].
GENTRY, LE ;
WEBB, NR ;
LIM, GJ ;
BRUNNER, AM ;
RANCHALIS, JE ;
TWARDZIK, DR ;
LIOUBIN, MN ;
MARQUARDT, H ;
PURCHIO, AF .
MOLECULAR AND CELLULAR BIOLOGY, 1987, 7 (10) :3418-3427
[12]  
IGNOTZ RA, 1986, J BIOL CHEM, V261, P4337
[13]  
JOYCE ME, 1990, ORTHOP CLIN N AM, V21, P199
[14]   DIFFERENTIAL EXPRESSION OF TRANSFORMING GROWTH FACTOR-ALPHA AND FACTOR-BETA IN RAT INTESTINAL EPITHELIAL-CELLS [J].
KOYAMA, S ;
PODOLSKY, DK .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (05) :1768-1773
[15]   EFFECTS OF GROWTH-FACTORS ON AN INTESTINAL EPITHELIAL-CELL LINE - TRANSFORMING GROWTH-FACTOR-BETA INHIBITS PROLIFERATION AND STIMULATES DIFFERENTIATION [J].
KUROKOWA, M ;
LYNCH, K ;
PODOLSKY, DK .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1987, 142 (03) :775-782
[16]   CLEAVAGE OF STRUCTURAL PROTEINS DURING ASSEMBLY OF HEAD OF BACTERIOPHAGE-T4 [J].
LAEMMLI, UK .
NATURE, 1970, 227 (5259) :680-+
[17]   AN ALPHA-2-MACROGLOBULIN RECEPTOR-DEPENDENT MECHANISM FOR THE PLASMA-CLEARANCE OF TRANSFORMING GROWTH FACTOR-BETA-1 IN MICE [J].
LAMARRE, J ;
HAYES, MA ;
WOLLENBERG, GK ;
HUSSAINI, I ;
HALL, SW ;
GONIAS, SL .
JOURNAL OF CLINICAL INVESTIGATION, 1991, 87 (01) :39-44
[18]   EVALUATION OF INVITRO BROMODEOXYURIDINE LABELING OF BREAST CARCINOMAS WITH THE USE OF A COMMERCIAL KIT [J].
LLOVERAS, B ;
EDGERTON, S ;
THOR, AD .
AMERICAN JOURNAL OF CLINICAL PATHOLOGY, 1991, 95 (01) :41-47
[19]   MECHANISM OF ACTIVATION OF LATENT RECOMBINANT TRANSFORMING GROWTH FACTOR-BETA-1 BY PLASMIN [J].
LYONS, RM ;
GENTRY, LE ;
PURCHIO, AF ;
MOSES, HL .
JOURNAL OF CELL BIOLOGY, 1990, 110 (04) :1361-1367
[20]   TRANSFORMING GROWTH FACTOR-BETA ACTIVITY IS POTENTIATED BY HEPARIN VIA DISSOCIATION OF THE TRANSFORMING GROWTH FACTOR-BETA ALPHA-2-MACROGLOBULIN INACTIVE COMPLEX [J].
MCCAFFREY, TA ;
FALCONE, DJ ;
BRAYTON, CF ;
AGARWAL, LA ;
WELT, FGP ;
WEKSLER, BB .
JOURNAL OF CELL BIOLOGY, 1989, 109 (01) :441-448