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Reduced migration, altered matrix and enhanced TGFbeta1 signaling are signatures of mouse keratinocytes lacking Sdc1.
J Cell Sci. 2007 Aug 15; 120(Pt 16):2851-63.JC

Abstract

We have reported previously that syndecan-1 (Sdc1)-null mice show delayed re-epithelialization after skin and corneal wounding. Here, we show that primary keratinocytes obtained from Sdc1-null mice and grown for 3-5 days in culture are more proliferative, more adherent and migrate more slowly than wt keratinocytes. However, the migration rates of Sdc1-null keratinocytes can be restored to wild-type levels by replating Sdc1-null keratinocytes onto tissue culture plates coated with fibronectin and collagen I, laminin (LN)-332 or onto the matrices produced by wild-type cells. Migration rates can also be restored by treating Sdc1-null keratinocytes with antibodies that block alpha6 or alphav integrin function, or with TGFbeta1. Antagonizing either beta1 integrin function using a function-blocking antibody or TGFbeta1 using a neutralizing antibody reduced wild-type keratinocyte migration more than Sdc1-null keratinocyte migration. Cultures of Sdc1-null keratinocytes accumulated less collagen than wild-type cultures but their matrices contained the same amount of LN-332. The Sdc1-null keratinocytes expressed similar total amounts of eight different integrin subunits but showed increased surface expression of alphavbeta6, alphavbeta8, and alpha6beta4 integrins compared with wild-type keratinocytes. Whereas wild-type keratinocytes increased their surface expression of alpha2beta1, alphavbeta6, alphavbeta8, and alpha6beta4 after treatment with TGFbeta1, Sdc1-null keratinocytes did not. Additional data from a dual-reporter assay and quantification of phosphorylated Smad2 show that TGFbeta1 signaling is constitutively elevated in Sdc1-null keratinocytes. Thus, our results identify TGFbeta1 signaling and Sdc1 expression as important factors regulating integrin surface expression, activity and migration in keratinocyte and provide new insight into the functions regulated by Sdc1.

Authors+Show Affiliations

Department of Anatomy and Cell Biology, George Washington University Medical School, Washington, DC 20037, USA. mastepp@gwu.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

17666434

Citation

Stepp, Mary Ann, et al. "Reduced Migration, Altered Matrix and Enhanced TGFbeta1 Signaling Are Signatures of Mouse Keratinocytes Lacking Sdc1." Journal of Cell Science, vol. 120, no. Pt 16, 2007, pp. 2851-63.
Stepp MA, Liu Y, Pal-Ghosh S, et al. Reduced migration, altered matrix and enhanced TGFbeta1 signaling are signatures of mouse keratinocytes lacking Sdc1. J Cell Sci. 2007;120(Pt 16):2851-63.
Stepp, M. A., Liu, Y., Pal-Ghosh, S., Jurjus, R. A., Tadvalkar, G., Sekaran, A., Losicco, K., Jiang, L., Larsen, M., Li, L., & Yuspa, S. H. (2007). Reduced migration, altered matrix and enhanced TGFbeta1 signaling are signatures of mouse keratinocytes lacking Sdc1. Journal of Cell Science, 120(Pt 16), 2851-63.
Stepp MA, et al. Reduced Migration, Altered Matrix and Enhanced TGFbeta1 Signaling Are Signatures of Mouse Keratinocytes Lacking Sdc1. J Cell Sci. 2007 Aug 15;120(Pt 16):2851-63. PubMed PMID: 17666434.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced migration, altered matrix and enhanced TGFbeta1 signaling are signatures of mouse keratinocytes lacking Sdc1. AU - Stepp,Mary Ann, AU - Liu,Yueyuan, AU - Pal-Ghosh,Sonali, AU - Jurjus,Rosalyn A, AU - Tadvalkar,Gauri, AU - Sekaran,Adith, AU - Losicco,Kristen, AU - Jiang,Li, AU - Larsen,Melinda, AU - Li,Luowei, AU - Yuspa,Stuart H, Y1 - 2007/07/31/ PY - 2007/8/2/pubmed PY - 2007/12/6/medline PY - 2007/8/2/entrez SP - 2851 EP - 63 JF - Journal of cell science JO - J Cell Sci VL - 120 IS - Pt 16 N2 - We have reported previously that syndecan-1 (Sdc1)-null mice show delayed re-epithelialization after skin and corneal wounding. Here, we show that primary keratinocytes obtained from Sdc1-null mice and grown for 3-5 days in culture are more proliferative, more adherent and migrate more slowly than wt keratinocytes. However, the migration rates of Sdc1-null keratinocytes can be restored to wild-type levels by replating Sdc1-null keratinocytes onto tissue culture plates coated with fibronectin and collagen I, laminin (LN)-332 or onto the matrices produced by wild-type cells. Migration rates can also be restored by treating Sdc1-null keratinocytes with antibodies that block alpha6 or alphav integrin function, or with TGFbeta1. Antagonizing either beta1 integrin function using a function-blocking antibody or TGFbeta1 using a neutralizing antibody reduced wild-type keratinocyte migration more than Sdc1-null keratinocyte migration. Cultures of Sdc1-null keratinocytes accumulated less collagen than wild-type cultures but their matrices contained the same amount of LN-332. The Sdc1-null keratinocytes expressed similar total amounts of eight different integrin subunits but showed increased surface expression of alphavbeta6, alphavbeta8, and alpha6beta4 integrins compared with wild-type keratinocytes. Whereas wild-type keratinocytes increased their surface expression of alpha2beta1, alphavbeta6, alphavbeta8, and alpha6beta4 after treatment with TGFbeta1, Sdc1-null keratinocytes did not. Additional data from a dual-reporter assay and quantification of phosphorylated Smad2 show that TGFbeta1 signaling is constitutively elevated in Sdc1-null keratinocytes. Thus, our results identify TGFbeta1 signaling and Sdc1 expression as important factors regulating integrin surface expression, activity and migration in keratinocyte and provide new insight into the functions regulated by Sdc1. SN - 0021-9533 UR - https://www.unboundmedicine.com/medline/citation/17666434/Reduced_migration_altered_matrix_and_enhanced_TGFbeta1_signaling_are_signatures_of_mouse_keratinocytes_lacking_Sdc1_ L2 - http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=17666434 DB - PRIME DP - Unbound Medicine ER -