scholarly journals Transcriptional Activation of the Matrix Metalloproteinase Gene stromelysin-3 Coincides with Thyroid Hormone-Induced Cell Death during Frog Metamorphosis

1995 ◽  
Vol 167 (1) ◽  
pp. 252-262 ◽  
Author(s):  
Danielle Patterton ◽  
William Pär Hayes ◽  
Yun-Bo Shi
Development ◽  
2002 ◽  
Vol 129 (6) ◽  
pp. 1487-1496 ◽  
Author(s):  
Lori M. Roberts ◽  
Jenny A. Visser ◽  
Holly A. Ingraham

Programmed cell death of the Müllerian duct eliminates the primitive female reproductive tract during normal male sexual differentiation. Müllerian inhibiting substance (MIS or AMH) triggers regression by propagating a BMP-like signaling pathway in the Müllerian mesenchyme that culminates in apoptosis of the Müllerian duct epithelium. Presently, the paracrine signal(s) used in this developmental event are undefined. We have identified a member of the matrix metalloproteinase gene family, Mmp2, as one of the first candidate target genes downstream of the MIS cascade to function as a paracrine death factor in Müllerian duct regression. Consistent with a role in regression, Mmp2 expression was significantly elevated in male but not female Müllerian duct mesenchyme. Furthermore, this sexually dimorphic expression of Mmp2 was extinguished in mice lacking the MIS ligand, suggesting strongly that Mmp2 expression is regulated by MIS signaling. Using rat organ genital ridge organ cultures, we found that inhibition of MMP2 activity prevented MIS-induced regression, whereas activation of MMP2 promoted ligand-independent Müllerian duct regression. Finally, MMP2 antisense experiments resulted in partial blockage of Müllerian duct regression. Based on our findings, we propose that similar to other developmental programs where selective elimination or remodeling of tissues occurs, localized induction of extracellular proteinases is critical for normal male urogenital development.


2009 ◽  
Vol 23 (8) ◽  
pp. 1255-1263 ◽  
Author(s):  
Christine E. Boumah ◽  
Minnkyong Lee ◽  
Nagarajan Selvamurugan ◽  
Emi Shimizu ◽  
Nicola C. Partridge

Oncogene ◽  
1997 ◽  
Vol 14 (16) ◽  
pp. 1995-1998 ◽  
Author(s):  
Bruce P Himelstein ◽  
Edward J Lee ◽  
Hiroshi Sato ◽  
Motoharu Seiki ◽  
Ruth J Muschel

2000 ◽  
Vol 150 (5) ◽  
pp. 1177-1188 ◽  
Author(s):  
Atsuko Ishizuya-Oka ◽  
Qing Li ◽  
Tosikazu Amano ◽  
Sashko Damjanovski ◽  
Shuichi Ueda ◽  
...  

The matrix metalloproteinase (MMP) stromelysin-3 (ST3) was originally discovered as a gene whose expression was associated with human breast cancer carcinomas and with apoptosis during organogenesis and tissue remodeling. It has been shown previously, in our studies as well as those by others, that ST3 mRNA is highly upregulated during apoptotic tissue remodeling during Xenopus laevis metamorphosis. Using a function-blocking antibody against the catalytic domain of Xenopus ST3, we demonstrate here that ST3 protein is specifically expressed in the cells adjacent to the remodeling extracellular matrix (ECM) that lies beneath the apoptotic larval intestinal epithelium in X. laevis in vivo, and during thyroid hormone–induced intestinal remodeling in organ cultures. More importantly, addition of this antibody, but not the preimmune antiserum or unrelated antibodies, to the medium of intestinal organ cultures leads to an inhibition of thyroid hormone–induced ECM remodeling, apoptosis of the larval epithelium, and the invasion of the adult intestinal primodia into the connective tissue, a process critical for adult epithelial morphogenesis. On the other hand, the antibody has little effect on adult epithelial cell proliferation. Furthermore, a known MMP inhibitor can also inhibit epithelial transformation in vitro. These results indicate that ST3 is required for cell fate determination and cell migration during morphogenesis, most likely through ECM remodeling.


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