Moyano, Jose V., Greciano, Patricia G., Buschmann, Mary M., Koch, Manuel ORCID: 0000-0002-2962-7814 and Matlin, Karl S. (2010). Autocrine Transforming Growth Factor-beta 1 Activation Mediated by Integrin alpha V beta 3 Regulates Transcriptional Expression of Laminin-332 in Madin-Darby Canine Kidney Epithelial Cells. Mol. Biol. Cell, 21 (21). S. 3654 - 3669. BETHESDA: AMER SOC CELL BIOLOGY. ISSN 1939-4586

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Abstract

Laminin (LM)-332 is an extracellular matrix protein that plays a structural role in normal tissues and is also important in facilitating recovery of epithelia from injury. We have shown that expression of LM-332 is up-regulated during renal epithelial regeneration after ischemic injury, but the molecular signals that control expression are unknown. Here, we demonstrate that in Madin-Darby canine kidney (MDCK) epithelial cells LM-332 expression occurs only in subconfluent cultures and is turned-off after a polarized epithelium has formed. Addition of active transforming growth factor (TGF)-beta 1 to confluent MDCK monolayers is sufficient to induce transcription of the LM alpha 3 gene and LM-332 protein expression via the TGF-beta type I receptor (T beta R-I) and the Smad2-Smad4 complex. Significantly, we show that expression of LM-332 in MDCK cells is an autocrine response to endogenous TGF-beta 1 secretion and activation mediated by integrin alpha V beta 3 because neutralizing antibodies block LM-332 production in subconfluent cells. In confluent cells, latent TGF-beta 1 is secreted apically, whereas T beta R-I and integrin alpha V beta 3 are localized basolaterally. Disruption of the epithelial barrier by mechanical injury activates TGF-beta 1, leading to LM-332 expression. Together, our data suggest a novel mechanism for triggering the production of LM-332 after epithelial injury.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Moyano, Jose V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Greciano, Patricia G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buschmann, Mary M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koch, ManuelUNSPECIFIEDorcid.org/0000-0002-2962-7814UNSPECIFIED
Matlin, Karl S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-493758
DOI: 10.1091/mbc.E10-06-0523
Journal or Publication Title: Mol. Biol. Cell
Volume: 21
Number: 21
Page Range: S. 3654 - 3669
Date: 2010
Publisher: AMER SOC CELL BIOLOGY
Place of Publication: BETHESDA
ISSN: 1939-4586
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GROWTH-FACTOR-BETA; TGF-BETA; BASEMENT-MEMBRANE; LAMININ-5-ENCODING GENES; ISCHEMIC-INJURY; RECEPTOR; MECHANISMS; DEPOSITION; PROMOTER; POLARITYMultiple languages
Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/49375

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