Pleiotrophin/heparin-binding growth-associated molecule as a mitogen of rat hepatocytes and its role in regeneration and development of liver.
Previously pleiotrophin (PTN) was identified among proteins secreted by Swiss 3T3 cells as a mitogen for cultured adult rat hepatocytes. The present study showed that the growth of rat hepatocytes was enhanced when cultured with rat hepatic stellate cells (HSCs). HSCs expressed PTN mRNA and secreted its protein in the co-cultures. Recombinant PTN enhanced the growth of hepatocytes in culture, suggesting that HSCs stimulate the growth of hepatocytes through the action of PTN. To know the biological role of PTN in the growth of hepatocytes in vivo, we examined the expression of PTN in four regeneration models of adult liver and embryonic liver of rat. The expression of PTN mRNA in the liver was markedly up-regulated by the treatment with D-galactosamine (GalN) or with acetylaminofluorene followed by partial hepatectomy. HSCs expressed PTN mRNA in response to GalN treatment and its protein was found on hepatocytes. The mRNA expression of N-syndecan, a PTN receptor, was up-regulated in GalN-treated hepatocytes. The mesenchymal cells in the septum transversum enclosing the embryonic liver, but not embryonic HSCs, expressed PTN mRNA. We suggest that PTN is secreted from activated adult HSCs and embryonic mesenchymal cells as a mitogen of parenchymal cells in adult and embryonic liver, respectively.
Asahina
Kinji
K
Hiroshima Tissue Regeneration Project, Hiroshima Prefecture Collaboration of Regional Entities for the Advancement of Technological Excellence, Japan Science and Technology Corporation, Hiroshima Prefectural Institute of Industrial Science and Technology.
Sato
Hajime
H
Yamasaki
Chihiro
C
Kataoka
Miho
M
Shiokawa
Miho
M
Katayama
Shigeru
S
Tateno
Chise
C
Yoshizato
Katsutoshi
K
D015073:2-Acetylaminofluorene / Q000494:pharmacology; D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000502:physiology*; D005688:Galactosamine / Q000494:pharmacology; D006498:Hepatectomy; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000254:growth & development*; D008115:Liver Regeneration / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000378:metabolism; D053670:Syndecan-3; D015854:Up-Regulation
D002352:Carrier Proteins; D016207:Cytokines; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; D011994:Recombinant Proteins; C508302:Sdc3 protein, mouse; C508303:Sdc3 protein, rat; D053670:Syndecan-3; C066845:pleiotrophin; D005688:Galactosamine; D015073:2-Acetylaminofluorene