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Literature summary for 3.4.22.27 extracted from

  • Kumar Vr, S.; Darisipudi, M.N.; Steiger, S.; Devarapu, S.K.; Tato, M.; Kukarni, O.P.; Mulay, S.R.; Thomasova, D.; Popper, B.; Demleitner, J.; Zuchtriegel, G.; Reichel, C.; Cohen, C.D.; Lindenmeyer, M.T.; Liapis, H.; Moll, S.; Reid, E.; Stitt, A.W.; Schott, B.; Gruner, S.; Haap, W.; Ebeling, M.; Hartmann, G.
    Cathepsin S cleavage of protease-activated receptor-2 on endothelial cells promotes microvascular diabetes complications (2016), J. Am. Soc. Nephrol., 27, 1635-1649 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.4.22.27

Application

Application Comment Organism
medicine Cat-S or PAR2 inhibition might be a strategy to prevent microvascular disease in diabetes and other diseases Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information generation of siRNA Cat-S knockout mice Mus musculus

Inhibitors

Inhibitors Comment Organism Structure
RO5461111
-
 Homo sapiens
RO5461111 inhibits Cat-S activity and reduces podocyte loss, proteinuria, glomerulosclerosis, and renal inflammation in T2D db/db mice Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
protease-activated receptor-2 + H2O Mus musculus
-
 ?
-
 ?
protease-activated receptor-2 + H2O Homo sapiens
-
 ?
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens P25774
-
-
Mus musculus O70370
-
-

Source Tissue

Source Tissue Comment Organism Textmining
endothelial cell
-
 Mus musculus
-
endothelial cell
-
 Homo sapiens
-
glomerular endothelial cell GEnC Homo sapiens
-
kidney
-
 Mus musculus
-
kidney
-
 Homo sapiens
-
macrophage cathepsin S is expressed by macrophages infiltrating the human kidney Homo sapiens
-
additional information in human type 2 diabetic nephropathy, only CD68+ intrarenal monocytes express Cat-S mRNA, whereasCat-S protein is present along endothelial cells and inside proximal tubular epithelial cells also Homo sapiens
-
additional information in mouse type 2 diabetic nephropathy, only CD68+ intrarenal monocytes express Cat-S mRNA, whereasCat-S protein is present along endothelial cells and inside proximal tubular epithelial cells also. Transcriptome analysis Mus musculus
-
podocyte
-
 Mus musculus
-
podocyte
-
 Homo sapiens
-
proximal tubular epithelial cell
-
 Mus musculus
-
proximal tubular epithelial cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
protease-activated receptor-2 + H2O
-
 Mus musculus ?
-
 ?
protease-activated receptor-2 + H2O
-
 Homo sapiens ?
-
 ?

Synonyms

Synonyms Comment Organism
Cat-S
-
 Mus musculus
Cat-S
-
 Homo sapiens
CTSS
-
 Mus musculus
CTSS
-
 Homo sapiens

General Information

General Information Comment Organism
malfunction in vitro transcriptome analysis and experiments using siRNA or specific Cat-S and PAR2 antagonists revealed that Cat-S specifically impaired the integrity and barrier function of glomerular endothelial cells selectively through PAR2 Mus musculus
malfunction in vitro transcriptome analysis and experiments using siRNA or specific Cat-S and PAR2 antagonists revealed that Cat-S specifically impaired the integrity and barrier function of glomerular endothelial cells selectively through PAR2. Extrinsic and intrinsic Cat-S triggers endothelial cell injury and microvascular permeability through PAR2 in vivo. Cat-S-induced monolayer disruption is prevented by Cat-S. Extrinsic and intrinsic Cat-S triggers endothelial cell injury and microvascular permeability through PAR2 in vivo Homo sapiens
physiological function cathepsin S (Cat-S) is a cysteine protease that degrades elastic fibers and activates the protease-activated receptor-2 (PAR2) on endothelial cells. Cathepsin S cleavage of protease-activated receptor-2 on endothelial cells promotes microvascular diabetes complications. Cat-S is a monocyte/macrophage-derived circulating PAR2 agonist and mediator of endothelial dysfunction-related microvascular diabetes complications. Extrinsic and intrinsic Cat-S triggers endothelial cell injury and microvascular permeability through PAR2 in vivo, Cat-S specifically induces GEnC dysfunction through PAR2 in vitro Homo sapiens
physiological function cathepsin S (Cat-S) is a cysteine protease that degrades elastic fibers and activates the protease-activated receptor-2 (PAR2) on endothelial cells. Cathepsin S cleavage of protease-activated receptor-2 on endothelial cells promotes microvascular diabetes complications. Cat-S is a monocyte/macrophage-derived circulating PAR2 agonist and mediator of endothelial dysfunction-related microvascular diabetes complications. In vitro transcriptome analysis and experiments using siRNA or specific Cat-S and PAR2 antagonists revealed that Cat-S specifically impaired the integrity and barrier function of glomerular endothelial cells selectively through PAR2. Delayed treatment of type 2 diabetic db/db mice with Cat-S or PAR2 inhibitors attenuates albuminuria and glomerulosclerosis (indicators of diabetic nephropathy) and attenuates albumin leakage into the retina and other structural markers of diabetic retinopathy Mus musculus