Molecular and cellular basis of the regulation of lymphatic contractility and lymphatic absorption.
Lymphatic absorption is a highly regulated process driven by both an extrinsic mechanism (external force) and an intrinsic mechanism (lymphatic vessel contractility). The lymphatic muscle is a specialized smooth muscle with unique mechanical properties. To understand the molecular mechanism and relative contribution of smooth muscle contraction in lymphatic absorption, we analyzed mice with a smooth muscle-specific deletion of Mylk, a critical gene for smooth muscle contraction. Interestingly, the knockout mice were significantly resistant to anesthesia reagents. Upon injection in the feet with FITC-dextran, the mutant mice displayed a 2-fold delay of the absorption peak in the peripheral circulation. Examining the ear lymphatic vessels of the mutant mice revealed a reduction in the amount of fluid in the lumens of the lymphangions, suggesting an impairment of lymph formation. The Mylk-deficient lymphatic muscle exhibited a significant reduction of peristalsis and of myosin light chain phosphorylation in response to depolarization. We thus concluded that MLCK and myosin light chain phosphorylation are required for lymphatic vessel contraction. Lymphatic contractility is not an exclusive requirement for lymphatic absorption, and external force appears to be necessary for absorption.
Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical College, Wenzhou, China; Jinhua Municipal Central Hospital, Jinhua, Zhejiang, China.
Yu
Y
Wang
Model Animal Research Center and MOE Key Laboratory of Animal Models of Disease, Nanjing University, Nanjing, China.
Wei
W
Zhao
Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical College, Wenzhou, China.
Lin
L
Zhang
Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical College, Wenzhou, China.
Yong-Na
YN
Zhao
Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical College, Wenzhou, China.
Fei
F
Li
Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical College, Wenzhou, China.
Zhen
Z
Zhang
Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical College, Wenzhou, China.
Yun-Dong
YD
Dai
Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical College, Wenzhou, China.
Wei-Feng
WF
Li
Model Animal Research Center and MOE Key Laboratory of Animal Models of Disease, Nanjing University, Nanjing, China.
Yan-Ning
YN
Qiao
Model Animal Research Center and MOE Key Laboratory of Animal Models of Disease, Nanjing University, Nanjing, China.
Cai-Ping
CP
Chen
Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical College, Wenzhou, China. Electronic address: jiminggao@yahoo.com.
Ji-Min
JM
Gao
Model Animal Research Center and MOE Key Laboratory of Animal Models of Disease, Nanjing University, Nanjing, China. Electronic address: zhums@nju.edu.cn.
Min-Sheng
MS
Zhu
D000818:Animals; D006801:Humans; D042601:Lymphatic Vessels / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009119:Muscle Contraction / Q000235:genetics*; D009130:Muscle, Smooth / Q000378:metabolism; D009154:Mutation; D018994:Myosin Light Chains / Q000235:genetics; D009219:Myosin-Light-Chain Kinase / Q000235:genetics* / Q000378:metabolism
D018994:Myosin Light Chains; D009219:Myosin-Light-Chain Kinase
Contractility, Absorption; Lymphatic vessel; Myosin light chain kinase; Smooth muscle