Unique expression patterns of matrix metalloproteinases in regenerating newt limbs

Abstract

The process of regeneration of urodele limbs includes a drastic remodeling of extracellular matrices (ECMs) that is induced by matrix metalloproteinases (MMPs) and is thought to be one of the triggers of the regeneration. We studied this remodeling in limbs of Japanese newt, Cynops pyrrhogaster, by using five genes of newt MMPs (nMMPs) as probes: nMMP9, nMMP3/10-a, nMMP3/10-b, and nMMP13 that had been characterized previously, and nMMPe that was newly cloned in the present study. nMMPe was 502 amino acid residues long and showed a low homology to other known vertebrate MMPs.

Looking proximally and distally: 100 years of limb regeneration and beyond

“…Up-regulated MMP transcripts include MMP-2 and À9 (gelatinases), and MMP-3/10a and b (stromelysins) (Grillo et al, 1968;Dresden and Gross, 1970;Yang and Bryant, 1994;Miyazaki et al, 1996;Ju and Kim, 1998;Yang et al, 1999;Park and Kim, 1999;Kato et al, 2003;Vinarsky et al, 2005). In the newt limb, the basal layer of the wound epidermis transcribes MMP3/ 10a and b, as well as a novel MMP with low homology to the others (Kato et al, 2003). Chondrocytes express MMP-2 and -9 transcripts in the newt limb, and these enzymes are proposed to diffuse outward from the degrading skeletal elements (Kato et al, 2003).…”

“…In the newt limb, the basal layer of the wound epidermis transcribes MMP3/ 10a and b, as well as a novel MMP with low homology to the others (Kato et al, 2003). Chondrocytes express MMP-2 and -9 transcripts in the newt limb, and these enzymes are proposed to diffuse outward from the degrading skeletal elements (Kato et al, 2003). An important function of the MMPs encoded by the basal layer of the wound epidermis is thought to be the prevention of basement membrane reassembly beneath it, thus maintaining communication between the wound epidermis and subjacent blastema cells.…”

Matrix metalloproteinase expression during blastema formation in regeneration‐competent versus regeneration‐deficient amphibian limbs

“…The major histolytic role played by MMPs, and the importance of histolysis to the success of regeneration have been emphasized by the failure of blastema formation in amputated newt limbs treated with the MMP inhibitor GM6001 (Vinarsky et al, 2005). MMP transcripts that have been identified in regenerating axolotl and newt limbs include the gelatinases MMP-2 and -9, and the stromelysins MMP-3/10a and b (Yang and Bryant, 1994;Miyazaki et al, 1996;Park and Kim, 1999;Kato et al, 2003;Vinarsky et al, 2005). Cells in the basal layer of the wound epidermis express MMP-3/ 10a and b transcripts in the regenerating newt limb, as well as transcripts of a novel MMP with low homology to other MMP transcripts (Kato et al, 2003).…”

“…MMP transcripts that have been identified in regenerating axolotl and newt limbs include the gelatinases MMP-2 and -9, and the stromelysins MMP-3/10a and b (Yang and Bryant, 1994;Miyazaki et al, 1996;Park and Kim, 1999;Kato et al, 2003;Vinarsky et al, 2005). Cells in the basal layer of the wound epidermis express MMP-3/ 10a and b transcripts in the regenerating newt limb, as well as transcripts of a novel MMP with low homology to other MMP transcripts (Kato et al, 2003). At the protein level, these MMPs may be responsible for maintaining contact between the wound epidermis and underlying tissues by preventing the re-formation of a basement membrane, as well as degrading other ECM components of these tissues.…”

“…Subsequently, numerous studies have demonstrated changes in the expression of various gelatinase and stromelysin transcripts during blastema formation in regenerating urodele (axolotl and newt) limbs. Transcripts for MMP-2, MMP-9, and MMP-3/-10 (Yang and Bryant, 1994;Miyazaki et al, 1996;Park and Kim, 1999;Kato et al, 2003;Vinarsky et al, 2005) are up-regulated during formation of the accumulation blastema. However, we have little information about individual MMP expression at the protein level during histolysis in regenerating limbs and neither MMP transcript nor protein expression has been compared in regeneration-competent vs. regeneration-deficient limbs.…”