Resolvin Conjugates in Tissue Regeneration 1 Promote Alveolar Fluid Clearance by Activating Alveolar Epithelial Sodium Channels and Na, K-ATPase in Lipopolysaccharide-Induced Acute Lung Injury.

Autor:	Yang Q; Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (Q.Y., H.X., S.X., Y.Y., C.S., H.M., P.Z., H.Ma, S.Z. F.S., S.J., Q.W.), and Wenzhou Medical University (C.Z.), Zhejiang, China; and Institute of Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (F.S.)., Xu HR; Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (Q.Y., H.X., S.X., Y.Y., C.S., H.M., P.Z., H.Ma, S.Z. F.S., S.J., Q.W.), and Wenzhou Medical University (C.Z.), Zhejiang, China; and Institute of Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (F.S.)., Xiang SY; Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (Q.Y., H.X., S.X., Y.Y., C.S., H.M., P.Z., H.Ma, S.Z. F.S., S.J., Q.W.), and Wenzhou Medical University (C.Z.), Zhejiang, China; and Institute of Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (F.S.)., Zhang C; Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (Q.Y., H.X., S.X., Y.Y., C.S., H.M., P.Z., H.Ma, S.Z. F.S., S.J., Q.W.), and Wenzhou Medical University (C.Z.), Zhejiang, China; and Institute of Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (F.S.)., Ye Y; Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (Q.Y., H.X., S.X., Y.Y., C.S., H.M., P.Z., H.Ma, S.Z. F.S., S.J., Q.W.), and Wenzhou Medical University (C.Z.), Zhejiang, China; and Institute of Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (F.S.)., Shen CX; Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (Q.Y., H.X., S.X., Y.Y., C.S., H.M., P.Z., H.Ma, S.Z. F.S., S.J., Q.W.), and Wenzhou Medical University (C.Z.), Zhejiang, China; and Institute of Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (F.S.)., Mei HX; Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (Q.Y., H.X., S.X., Y.Y., C.S., H.M., P.Z., H.Ma, S.Z. F.S., S.J., Q.W.), and Wenzhou Medical University (C.Z.), Zhejiang, China; and Institute of Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (F.S.)., Zhang PH; Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (Q.Y., H.X., S.X., Y.Y., C.S., H.M., P.Z., H.Ma, S.Z. F.S., S.J., Q.W.), and Wenzhou Medical University (C.Z.), Zhejiang, China; and Institute of Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (F.S.)., Ma HY; Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (Q.Y., H.X., S.X., Y.Y., C.S., H.M., P.Z., H.Ma, S.Z. F.S., S.J., Q.W.), and Wenzhou Medical University (C.Z.), Zhejiang, China; and Institute of Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (F.S.)., Zheng SX; Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (Q.Y., H.X., S.X., Y.Y., C.S., H.M., P.Z., H.Ma, S.Z. F.S., S.J., Q.W.), and Wenzhou Medical University (C.Z.), Zhejiang, China; and Institute of Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (F.S.)., Smith FG; Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (Q.Y., H.X., S.X., Y.Y., C.S., H.M., P.Z., H.Ma, S.Z. F.S., S.J., Q.W.), and Wenzhou Medical University (C.Z.), Zhejiang, China; and Institute of Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (F.S.)., Jin SW; Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (Q.Y., H.X., S.X., Y.Y., C.S., H.M., P.Z., H.Ma, S.Z. F.S., S.J., Q.W.), and Wenzhou Medical University (C.Z.), Zhejiang, China; and Institute of Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (F.S.) jsw@wmu.edu.cn wqian84@163.com., Wang Q; Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (Q.Y., H.X., S.X., Y.Y., C.S., H.M., P.Z., H.Ma, S.Z. F.S., S.J., Q.W.), and Wenzhou Medical University (C.Z.), Zhejiang, China; and Institute of Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (F.S.) jsw@wmu.edu.cn wqian84@163.com.
Jazyk:	angličtina
Zdroj:	The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2021 Nov; Vol. 379 (2), pp. 156-165. Date of Electronic Publication: 2021 Aug 31.
DOI:	10.1124/jpet.121.000712
Abstrakt:	Acute respiratory distress syndrome (ARDS), a common and fatal clinical condition, is characterized by the destruction of epithelium and augmented permeability of the alveolar-capillary barrier. Resolvin conjugates in tissue regeneration 1 (RCTR1) is an endogenous lipid mediator derived from docosahexaenoic acid , exerting proresolution effects in the process of inflammation. In our research, we evaluated the role of RCTR1 in alveolar fluid clearance (AFC) in lipopolysaccharide-induced ARDS/acute lung injury (ALI) rat model. Rats were injected with RCTR1 (5 μg/kg) via caudal veins 8 hours after lipopolysaccharide (LPS) (14 mg/kg) treatment, and then AFC was estimated after 1 hour of ventilation. Primary type II alveolar epithelial cells were incubated with LPS (1 ug/ml) with or without RCTR1 (10 nM) for 8 hours. Our results showed that RCTR1 significantly enhanced the survival rate, promoted the AFC, and alleviated LPS-induced ARDS/ALI in vivo. Furthermore, RCTR1 remarkably elevated the protein expression of sodium channels and Na, K-ATPase and the activity of Na, K-ATPase in vivo and in vitro. Additionally, RCTR1 also decreased neural precursor cell expressed developmentally downregulated 4-2 (Nedd4-2) level via upregulating Ser 473 -phosphorylated-Akt expression. Besides this, inhibitors of receptor for lipoxin A4 (ALX), cAMP, and phosphatidylinositol 3-kinase (PI3K) (BOC-2, KH-7, and LY294002) notably inhibited the effects of RCTR1 on AFC. In summary, RCTR1 enhances the protein levels of sodium channels and Na, K-ATPase and the Na, K-ATPase activity to improve AFC in ALI through ALX/cAMP/PI3K/Nedd4-2 pathway, suggesting that RCTR1 may become a therapeutic drug for ARDS/ALI. SIGNIFICANCE STATEMENT: RCTR1, an endogenous lipid mediator, enhanced the rate of AFC to accelerate the resolution of inflammation in the LPS-induced murine lung injury model. RCTR1 upregulates the expression of epithelial sodium channels (ENaCs) and Na, K-ATPase in vivo and in vitro to accelerate the AFC. The efficacy of RCTR1 on the ENaC and Na, K-ATPase level was in an ALX/cAMP/PI3K/Nedd4-2-dependent manner. (Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu