Activation of wound healing in aged rats by altering the cellular mitogenic potential.
We previously showed that lysophosphatidic acid (LPA) and an adenylyl cyclase inhibitor (ACI) stimulate mitogenic activation of senescent human diploid fibroblasts. Because the modulation of cell proliferation may affect wound healing in aged organisms, we studied the effects of LPA and ACI on in vivo skin wound healing in aged Fisher 344 rats. We found that, in aged rats, wound healing improved in animals treated with LPA and/or ACI (relative to untreated controls), as assessed by histological analysis of reepithelialization and immunostaining for proliferating cell nuclear antigen. The age-dependent activation of mitogenic responses by LPA and ACI was confirmed in other cell types. Taken together, our findings suggest that the activation of mitogenic potential in senescent cells by LPA and/or ACI may translate into enhanced in vivo wound healing and tissue regeneration in aged animals.
Rhim
Ji Heon
JH
Department of Biochemistry and Molecular Biology, Ageing and Apoptosis Research Center, Seoul National University College of Medicine, 28 Yon-gon-Dong, Chongno-Gu, Seoul 110-799, South Korea.
Jang
Ik-Soon
IS
Kwon
Sung Tack
ST
Song
Kye Yong
KY
Yeo
Eui-Ju
EJ
Park
Sang Chul
SC
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000367:Age Factors; D000375:Aging / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D008938:Mitosis / Q000187:drug effects*; D018809:Proliferating Cell Nuclear Antigen / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012867:Skin / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects*
D000067956:Adenylyl Cyclase Inhibitors; D008246:Lysophospholipids; D018809:Proliferating Cell Nuclear Antigen; C017759:9-(tetrahydro-2-furyl)-adenine; D020794:Receptor Protein-Tyrosine Kinases; D000225:Adenine; C032881:lysophosphatidic acid