title: Water-extracted Perilla frutescens increases endometrial receptivity though leukemia inhibitory factor-dependent expression of integrins.
abstract: The leaves and stems of Perilla frutescens var. acuta Kudo (PF) have been used to prevent threatened abortion in traditional medicine in the East Asian countries. Because reduced receptivity of endometrium is a cause of abortion, we analyzed the action of PF on the endometrial receptivity. PF increased the level of leukemia inhibitory factor (LIF), a major cytokine regulating endometrial receptivity, and LIF receptor in human endometrial Ishikawa cells. The PF-induced LIF expression was mediated by c-jun N-terminal kinase (JNK) and p38 pathways. Adhesion between Ishikawa cells and trophoblastic JAr cells stimulated by PF treatment was abolished by knock down of LIF expression or antagonism of LIFR. In addition, the expressions of integrin β3 and β5 were increased by PF treatment in Ishikawa cells. The PF-induced expression of integrin β3 and β5 was reduced with an LIFR antagonist. Neutralization of both integrins successfully blocked PF-stimulated adhesion of JAr cells and Ishikawa cells. These results suggest that PF enhanced the adhesion between Ishikawa cells and JAr cells by increasing the expression of integrin β3 and β5 via an LIF-dependent pathway. Given the importance of endometrial receptivity in successful pregnancy, PF can be a novel and effective candidate for improving pregnancy rate.
authors: School of Korean Medicine and Healthy Aging Korean Medical Research Center, Pusan National University, Busandaehak-ro 49, Mulgeum-eup, Yangsan, Gyeongsangnam-do 50612, Republic of Korea.
authors: Eun-Yeong
authors: EY
authors: Kim
authors: School of Korean Medicine and Healthy Aging Korean Medical Research Center, Pusan National University, Busandaehak-ro 49, Mulgeum-eup, Yangsan, Gyeongsangnam-do 50612, Republic of Korea.
authors: Hee-Jung
authors: HJ
authors: Choi
authors: School of Korean Medicine and Healthy Aging Korean Medical Research Center, Pusan National University, Busandaehak-ro 49, Mulgeum-eup, Yangsan, Gyeongsangnam-do 50612, Republic of Korea.
authors: Tae-Wook
authors: TW
authors: Chung
authors: School of Korean Medicine and Healthy Aging Korean Medical Research Center, Pusan National University, Busandaehak-ro 49, Mulgeum-eup, Yangsan, Gyeongsangnam-do 50612, Republic of Korea; National Clinical Research Center for Korean Medicine, Korean Medicine Hospital of Pusan National University, Geumo-ro 20, Mulgeum-eup, Yangsan, Gyeongsangnam-do 50612, Republic of Korea.
authors: Jun-Yong
authors: JY
authors: Choi
authors: Laboratory of Molecular Toxicology, School of Pharmacy, SungKyunKwan University, Seobu-ro 2066, Jangan-gu, Suwon, Gyeonggi-do 16419, Republic of Korea.
authors: Hyung Sik
authors: HS
authors: Kim
authors: Department of Food Science and Technology, Keimyung University, Dalgubeoldae-ro 1095, Dalseo-gu, Daegu 42601, Republic of Korea.
authors: Yeon-Seop
authors: YS
authors: Jung
authors: Department of Food Science and Technology, Keimyung University, Dalgubeoldae-ro 1095, Dalseo-gu, Daegu 42601, Republic of Korea.
authors: Syng-Ook
authors: SO
authors: Lee
authors: School of Korean Medicine and Healthy Aging Korean Medical Research Center, Pusan National University, Busandaehak-ro 49, Mulgeum-eup, Yangsan, Gyeongsangnam-do 50612, Republic of Korea; National Clinical Research Center for Korean Medicine, Korean Medicine Hospital of Pusan National University, Geumo-ro 20, Mulgeum-eup, Yangsan, Gyeongsangnam-do 50612, Republic of Korea. Electronic address: hagis@pusan.ac.kr.
authors: Ki-Tae
authors: KT
authors: Ha
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004717:Endometrium / Q000187:drug effects*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D039641:Integrin beta Chains / Q000096:biosynthesis* / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009570:Nitriles / Q000494:pharmacology; D031344:Perilla frutescens / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D011725:Pyridines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000873:Anthracenes; D002070:Butadienes; D007093:Imidazoles; D039641:Integrin beta Chains; C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D009570:Nitriles; D010936:Plant Extracts; D011725:Pyridines; D034741:RNA, Small Interfering; C113580:U 0126; C432165:pyrazolanthrone; C093642:SB 203580
keywords: Endometrial receptivity; Infertility; Integrin; LIF; Perilla frutescens