Protean proteases: at the cutting edge of lung diseases.
Proteases were traditionally viewed as mere protein-degrading enzymes with a very restricted spectrum of substrates. A major expansion in protease research has uncovered a variety of novel substrates, and it is now evident that proteases are critical pleiotropic actors orchestrating pathophysiological processes. Recent findings evidenced that the net proteolytic activity also relies upon interconnections between different protease and protease inhibitor families in the protease web.In this review, we provide an overview of these novel concepts with a particular focus on pulmonary pathophysiology. We describe the emerging roles of several protease families including cysteine and serine proteases.The complexity of the protease web is exemplified in the light of multidimensional regulation of serine protease activity by matrix metalloproteases through cognate serine protease inhibitor processing. Finally, we will highlight how deregulated protease activity during pulmonary pathogenesis may be exploited for diagnosis/prognosis purposes, and utilised as a therapeutic tool using nanotechnologies.Considering proteases as part of an integrative biology perspective may pave the way for the development of new therapeutic targets to treat pulmonary diseases related to intrinsic protease deregulation.
Airway Innate Immunity Research group (AiiR), Centre for Experimental Medicine, Queen's University Belfast, UK.
Clifford
C
Taggart
Dept of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany.|Division of Pediatric Pulmonology & Allergy and Cystic Fibrosis Center, Dept of Pediatrics, University of Heidelberg, Heidelberg, Germany.|Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany.
Marcus A
MA
Mall
INSERM UMR1100 Centre d'Etude des Pathologies Respiratoires (CEPR), Equipe: Mécanismes Protéolytiques dans l'Inflammation, Université François Rabelais, Tours, France.
Gilles
G
Lalmanach
Laboratory of Tumors and Development and Dept of Respiratory Diseases, University of Liege, Liege, Belgium.
Didier
D
Cataldo
Inflammation Pharmacology Research Group, Institute of Pharmacology and Toxicology, RWTH Aachen University, Aachen, Germany.
Andreas
A
Ludwig
Dept of Respiratory Medicine, a member of The German Center for Lung Research (DZL), Hannover Medical School, Hannover, Germany.
Sabina
S
Janciauskiene
Division of Pediatric Pulmonology & Allergy and Cystic Fibrosis Center, Dept of Pediatrics, University of Heidelberg, Heidelberg, Germany.|Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany.|European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
Nicole
N
Heath
Comprehensive Pneumology Center (CPC), University Hospital, Ludwig-Maximilians University, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
Silke
S
Meiners
Centre for Blood Research, Dept of Oral Biological and Medical Research University of British Columbia, Vancouver, BC, Canada.
Christopher M
CM
Overall
Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany.|European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
Carsten
C
Schultz
Dept of Biochemistry & Molecular & Structural Biology, J. Stefan Institute, Ljubljana, Slovenia.
Boris
B
Turk
INSERM UMR _S933, Université Pierre et Marie Curie, Paris, France keren.borensztajn@inserm.fr.|INSERM UMR1152 Université Paris Diderot, Faculté de Médecine - site Bichat, Paris, France.
Keren S
KS
Borensztajn
D000818:Animals; D006801:Humans; D008168:Lung / Q000201:enzymology* / Q000276:immunology; D008171:Lung Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D011480:Protease Inhibitors / Q000627:therapeutic use; D059748:Proteolysis / Q000187:drug effects
D011480:Protease Inhibitors; D020782:Matrix Metalloproteinases