title: Immunophenotypical analyses of myofibroblasts in rat excisional wound healing: possible transdifferentiation of blood vessel pericytes and perifollicular dermal sheath cells into myofibroblasts.
abstract: Cutaneous fibrosis after wound is evoked by myofibroblasts capable of producing collagen; the derivation and features remain to be investigated. Immunophenotypical characteristics of myofibroblasts were analysed in excisional rat wound healing, of which samples were obtained on post-wounding (PW) days 1 to 26. Myofibroblasts were characterized for expressions of intermediate cytoskeletons such as vimentin, desmin, and α-smooth muscle actin (α-SMA). To pursue the progenitor, immunolabeling analyses were performed using stromal-/bone marrow-stem cell markers (Thy-1 and A3). Myofibroblasts reacting to vimentin and α-SMA were first seen on PW day 5, then peaked on PW day 9 in granulation tissues, and gradually decreased in remodeling tissues; these immunopositive cells reacted simultaneously to Thy-1. Desmin-reacting cells were limited to newly-formed blood vessels in wound bed. The single/double immunolabelings revealed that pericytes (identified by positive reaction to PDGFR-β and negative reaction to endothelial markers) in newly-developing blood vessels reacted to vimentin, α-SMA, Thy-1 and A3, and occasionally to desmin, and that perifollicular dermal sheath cells in the wound periphery showed increased expressions for vimentin, Thy-1 and A3. There is considerable immunophenotypical similarity between myofibroblasts (expressing vimentin, α-SMA and Thy-1), pericytes (reacting to vimentin, α-SMA, Thy-1 and A3) in newly-developing blood vessels, and perifollicular dermal sheath cells (reacting to vimentin, Thy-1 and A3). Collectively, myofibroblasts in rat cutaneous fibrosis are characterized by vimentin, α-SMA and Thy-1 expressions, and the cells might be generated from the pericytes or perifollicular dermal sheath cells in the lineage of stroma-/bone marrow-stem cells.
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan.
authors.forename: V
authors.initials: V
authors.lastname: Juniantito
authors.forename: T
authors.initials: T
authors.lastname: Izawa
authors.forename: T
authors.initials: T
authors.lastname: Yuasa
authors.forename: C
authors.initials: C
authors.lastname: Ichikawa
authors.forename: E
authors.initials: E
authors.lastname: Yamamoto
authors.forename: M
authors.initials: M
authors.lastname: Kuwamura
authors.forename: J
authors.initials: J
authors.lastname: Yamate
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D054338:Cell Transdifferentiation / Q000502:physiology*; D020405:Dermis / Q000166:cytology* / Q000378:metabolism; D003893:Desmin / Q000378:metabolism; D004195:Disease Models, Animal; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism; D008297:Male; D058628:Myofibroblasts / Q000166:cytology* / Q000378:metabolism; D020286:Pericytes / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D018800:Thy-1 Antigens / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D000199:Actins; D015415:Biomarkers; D003893:Desmin; D018800:Thy-1 Antigens; D014746:Vimentin; D020797:Receptor, Platelet-Derived Growth Factor beta