HIP/PAP stimulates liver regeneration after partial hepatectomy and combines mitogenic and anti-apoptotic functions through the PKA signaling pathway Export

@article{Simon2003, abstract = {The HIP/PAP (=human Reg-2) C-type lectin encoding gene is activated in primary liver cancers. In normal liver, the protein is undetectable in normal mature hepatocytes and found only in some ductular cells, representing potential hepatic progenitor cells. The aim of this study was to examine the consequences of human HIP/PAP expression in the liver of transgenic mice. We demonstrated that HIP/PAP stimulated liver regeneration after partial hepatectomy. To further investigate the enhanced liver regeneration observed in vivo, primary cultures of hepatocytes were used to evaluate the mitogenic and anti-apoptotic properties of HIP/PAP. HIP/PAP increased hepatocyte DNA synthesis and protected hepatocytes against TNF-alpha plus actinomycin-D-induced apoptosis. HIP/PAP anti-apoptotic effects against TNF-alpha were clearly demonstrated when protein kinase A activity was specifically inhibited by KT5720, and HIP/PAP stimulated PKA-dependent phosphorylation of the proapoptotic Bad protein at Ser-112, suggesting that HIP/PAP may compete with cAMP to stimulate PKA activity. Overall, our results led us to propose a new role for a C-type lectin, HIP/PAP, as a hepatic cytokine that combines mitogenic and anti-apoptotic functions regarding hepatocytes, and consequently acts as a growth factor in vivo to enhance liver regeneration.--Simon, M.-T., Pauloin, A., Normand, G., Lieu, H.-T., Mouly, H., Pivert, G., Carnot, F., Tralhao, J. G., Brechot, C., Christa, L. HIP/PAP stimulates liver regeneration after partial hepatectomy and combines mitogenic and anti-apoptotic functions through the PKA signaling pathway. 10.1096/fj.02-1013com}, author = {Simon, Marie-Therese and Pauloin, Alain and Normand, Guillaume and Lieu, Hanh-Tu and Mouly, Helene and Pivert, Gerard and Carnot, Francoise and Tralhao, Guilherme J. and Brechot, Christian and Christa, Laurence}, citeulike-article-id = {882519}, citeulike-linkout-0 = {http://www.fasebj.org/cgi/content/abstract/17/11/1441}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/12890698}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=12890698}, day = {1}, journal = {FASEB J.}, keywords = {function, hip, pap, pka, signal}, month = {August}, number = {11}, pages = {1441--1450}, posted-at = {2006-10-03 10:46:50}, priority = {2}, title = {HIP/PAP stimulates liver regeneration after partial hepatectomy and combines mitogenic and anti-apoptotic functions through the PKA signaling pathway}, url = {http://www.fasebj.org/cgi/content/abstract/17/11/1441}, volume = {17}, year = {2003} }

TY - JOUR ID - Simon2003 L3 - citeulike-article-id:882519 N2 - The HIP/PAP (=human Reg-2) C-type lectin encoding gene is activated in primary liver cancers. In normal liver, the protein is undetectable in normal mature hepatocytes and found only in some ductular cells, representing potential hepatic progenitor cells. The aim of this study was to examine the consequences of human HIP/PAP expression in the liver of transgenic mice. We demonstrated that HIP/PAP stimulated liver regeneration after partial hepatectomy. To further investigate the enhanced liver regeneration observed in vivo, primary cultures of hepatocytes were used to evaluate the mitogenic and anti-apoptotic properties of HIP/PAP. HIP/PAP increased hepatocyte DNA synthesis and protected hepatocytes against TNF-alpha plus actinomycin-D-induced apoptosis. HIP/PAP anti-apoptotic effects against TNF-alpha were clearly demonstrated when protein kinase A activity was specifically inhibited by KT5720, and HIP/PAP stimulated PKA-dependent phosphorylation of the proapoptotic Bad protein at Ser-112, suggesting that HIP/PAP may compete with cAMP to stimulate PKA activity. Overall, our results led us to propose a new role for a C-type lectin, HIP/PAP, as a hepatic cytokine that combines mitogenic and anti-apoptotic functions regarding hepatocytes, and consequently acts as a growth factor in vivo to enhance liver regeneration.--Simon, M.-T., Pauloin, A., Normand, G., Lieu, H.-T., Mouly, H., Pivert, G., Carnot, F., Tralhao, J. G., Brechot, C., Christa, L. HIP/PAP stimulates liver regeneration after partial hepatectomy and combines mitogenic and anti-apoptotic functions through the PKA signaling pathway. 10.1096/fj.02-1013com IS - 11 JF - FASEB J. EP - 1450 TI - HIP/PAP stimulates liver regeneration after partial hepatectomy and combines mitogenic and anti-apoptotic functions through the PKA signaling pathway VL - 17 SP - 1441 KW - function KW - hip KW - pap KW - pka KW - signal AU - Simon, Marie-Therese AU - Pauloin, Alain AU - Normand, Guillaume AU - Lieu, Hanh-Tu AU - Mouly, Helene AU - Pivert, Gerard AU - Carnot, Francoise AU - Tralhao, Guilherme AU - Brechot, Christian AU - Christa, Laurence PY - 2003/08/01/ UR - http://www.fasebj.org/cgi/content/abstract/17/11/1441 ER -