title: Stromal cell-derived factor-1α attenuates oleate-induced acute lung injury in rabbits.
abstract: The stromal cell-derived factor-1α/C-X-C chemokine receptor 4 (SDF-1/CXCR4) axis is involved in various aspects of tissue repair, regeneration and development. However, the role of SDF-1/CXCR4 in acute lung injury (ALI) remains largely unknown. The aim of the present investigation is to examine pathological changes in a rabbit model with ALI induced by oleic acid (OA) and to explore the protective effect of SDF-1α on ALI. Intravenous application (i.v.) of oleic acid (0.1 ml/kg/h for 2h) provoked pulmonary hemorrhage, edema, and protein leakage, resulting in severe ALI. When the rabbit received an infusion of SDF-1α (20 μg/kg/24h) for 30 min before OA treatment, SDF-1α seemed to significantly improve the pathologies associated with OA-induced ALI. While dissecting the molecular mechanisms underlying the beneficial effects of SDF-1α, we found that SDF-1/CXCR4 is expressed in uninjured lung tissues but is greatly reduced after OA treatment. Interestingly, intravenous delivery of SDF-1α could target an injured lung and rescue expression of CXCR4, which in turn activates anti-apoptotic proteins, Bcl-1 and Bcl-xl, but does not affect pro-apoptotic proteins, such as Bad and Bax. These data suggested that SDF-1α could protect rabbit lungs from AIL. The molecular mechanism might be associated with upregulating anti-apoptosis family expression through CXCR4. Thus, SDF-1/CXCR4 signaling pathway may be a promising target for treatment of patients with ALI.
authors.affiliation: Guangdong Geriatrics Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, No. 106 Zhongshan Road, Guangzhou 510100, China.
authors.forename: Weixin
authors.initials: W
authors.lastname: Guo
authors.affiliation: Division of General Surgery, Chenzhou First People's Hospital, Chenzhou, Hunan 423000, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Geriatrics, Tongji Hospital, Tongji University, School of Medicine, Shanghai 200065, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States.
authors.forename: Tao
authors.initials: T
authors.lastname: Tan
authors.affiliation: Guangdong Geriatrics Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, No. 106 Zhongshan Road, Guangzhou 510100, China.
authors.forename: Shouhong
authors.initials: S
authors.lastname: Wang
authors.affiliation: Division of Geriatrics, Tongji Hospital, Tongji University, School of Medicine, Shanghai 200065, China.
authors.forename: Nanzi
authors.initials: N
authors.lastname: Xie
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States.
authors.forename: Minghuan
authors.initials: M
authors.lastname: Fu
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Guangdong Geriatrics Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, No. 106 Zhongshan Road, Guangzhou 510100, China. Electronic address: tieheqin@126.com.
authors.forename: Tiehe
authors.initials: T
authors.lastname: Qin
mesh_terms: D000818:Animals; D054377:Chemokine CXCL12 / Q000502:physiology*; D008168:Lung / Q000187:drug effects*; D019301:Oleic Acid / Q000633:toxicity*; D011817:Rabbits
chemical_list: D054377:Chemokine CXCL12; D019301:Oleic Acid
keywords: Acute lung injury; Bcl-2; Bcl-xl; CXCR4; SDF-1