The Transmembrane Serine Protease HAT-like 4 Is Important for Epidermal Barrier Function to Prevent Body Fluid Loss.
Membrane-bound proteases are essential for epidermal integrity. Human airway trypsin-like protease 4 (HAT-L4) is a type II transmembrane serine protease. Currently, its biochemical property, cellular distribution and physiological function remain unknown. Here we examined HAT-L4 expression and function in vitro and in vivo. In Western analysis, HAT-L4 expressed in transfected CHO cells appeared as a 48-kDa protein. Flow cytometry confirmed HAT-L4 expression on the cell surface with the expected membrane topology. RT-PCR and immunostaining experiments indicated that HAT-L4 was expressed in epithelial cells and exocrine glands in tissues including skin, esophagus, trachea, tongue, eye, bladder, testis and uterus. In the skin, HAT-L4 expression was abundant in keratinocytes and sebaceous glands. We generated HAT-L4 knockout mice by disrupting the Tmprss11f gene encoding HAT-L4. HAT-L4 knockout mice were viable and fertile. No defects were found in HAT-L4 knockout mice in hair growth, wound healing, water repulsion and body temperature regulation. Compared with wild-type controls, HAT-L4-deficient newborn mice had greater body fluid loss and higher mortality in a trans-epidermal body fluid loss test. In metabolic studies, HAT-L4-deficient adult mice drank water more frequently than wild-type controls did. These results indicate that HAT-L4 is important in epidermal barrier function to prevent body fluid loss.
Cyrus Tang Hematology Center, MOE Engineering Center of Hematological Disease, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
Zhiwei
Z
Zhang
Cyrus Tang Hematology Center, MOE Engineering Center of Hematological Disease, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
Yae
Y
Hu
Cyrus Tang Hematology Center, MOE Engineering Center of Hematological Disease, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
Ruhong
R
Yan
Cyrus Tang Hematology Center, MOE Engineering Center of Hematological Disease, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
Liang
L
Dong
Cyrus Tang Hematology Center, MOE Engineering Center of Hematological Disease, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.|MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, China.
Yizhi
Y
Jiang
Cyrus Tang Hematology Center, MOE Engineering Center of Hematological Disease, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.|MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, China.
Zhichao
Z
Zhou
Cyrus Tang Hematology Center, MOE Engineering Center of Hematological Disease, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
Meng
M
Liu
Cyrus Tang Hematology Center, MOE Engineering Center of Hematological Disease, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
Tiantian
T
Zhou
Cyrus Tang Hematology Center, MOE Engineering Center of Hematological Disease, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.|MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, China.
Ningzheng
N
Dong
Cyrus Tang Hematology Center, MOE Engineering Center of Hematological Disease, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.|Molecular Cardiology, Cleveland Clinic, Cleveland, Ohio, USA.
Qingyu
Q
Wu
D000818:Animals; D000831:Animals, Newborn; D001826:Body Fluids / Q000378:metabolism*; D001833:Body Temperature Regulation; D016466:CHO Cells; D002460:Cell Line; D003412:Cricetulus; D004817:Epidermis / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism*; D057057:Serine Proteases / Q000235:genetics* / Q000378:metabolism*; D014018:Tissue Distribution
D008565:Membrane Proteins; D057057:Serine Proteases; D012697:Serine Endopeptidases; C000629131:TMPRSS11F protein, human; C000629132:Tmprss11f protein, mouse