COPASI36
fast: false
reversible: false
name: reaction_24
type: Reaction

COPASI22
fast: false
reversible: false
name: reaction_10
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000447#bc99a80b_0f6e_489f_ba14_2fdcc81d1354
stoichiometry: 1.0
species: COPASI4
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#_56dc76ba_d3e1_4d89_b31f_2aa8f7a417eb
constant: true
value: 0.07
name: k7
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000447#_7eb0cf16_7092_4595_a583_0818565d076c
constant: true
value: 0.0245
name: k_3
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000447#e5d41f55_cbd8_4120_875a_e9ccb17978c6
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
name: TSP1:PLS
type: Species

http://identifiers.org/biomodels.db/BIOMD0000000447#e7b30801_96ec_4b39_917e_5e87cbe94e80
stoichiometry: 1.0
species: COPASI3
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#_3e5f602e_dca6_423a_8f3f_0e4d886b3821
stoichiometry: 1.0
type: SpeciesReference

COPASI35
fast: false
reversible: false
name: reaction_23
type: Reaction

COPASI21
fast: false
type: Reaction
name: reaction_9
reversible: true

http://identifiers.org/biomodels.db/BIOMD0000000447#_2b6b23e1_75a8_45d6_ab54_f8e4d53aa3ec
constant: true
value: 0.0525
name: u_edeg
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000447#dfbc20da_6d50_499f_a794_23555403bc83
constant: true
value: 0.0035
name: alpha1
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000447#c8d93546_c77c_4b13_8977_998f187e7c6e
constant: true
value: 24.5
name: k8
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000447#_39b2013e_d66c_4c87_8415_e8f909c85bc0
constant: true
value: 0.0035
name: k_6
type: Parameter

COPASI34
fast: false
reversible: false
name: reaction_22
type: Reaction

COPASI24
name: reaction_12
reversible: true
type: Reaction
fast: false

http://identifiers.org/biomodels.db/BIOMD0000000447#d1a0a681_155b_4c90_a69c_a5c31f359fc6
constant: true
value: 1.05
name: kp2
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000447#fe910d7b_d329_488e_b101_00d5390a1cac
stoichiometry: 1.0
species: COPASI3
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#_50941eb8_5c69_40b1_95c3_36bc234937f3
constant: true
value: 0.005
name: kothers
type: Parameter

BIOMD0000000447
reaction: COPASI40
reaction: COPASI36
time units: metaid_0000010
species: COPASI8
reaction: COPASI41
reaction: COPASI25
parameter: COPASI11
reaction: COPASI15
species: COPASI9
reaction: COPASI37
notes: Venkatraman2012 - Interplay between PLS and TSP1 in TGF-β1 activation The interplay between PLS (Plasmin) and TSP1 (Thrombospondin-1) in TGF-β1 (Transforming growth factor-β1)is shown using mathematical modelling and in vitro experimentents. This model is described in the article: Plasmin triggers a switch-like decrease in thrombospondin-dependent activation of TGF-β1. Venkatraman L, Chia SM, Narmada BC, White JK, Bhowmick SS, Forbes Dewey C Jr, So PT, Tucker-Kellogg L, Yu H. Biophys J. 2012 Sep 5;103(5):1060-8. Abstract: Transforming growth factor-β1 (TGF-β1) is a potent regulator of extracellular matrix production, wound healing, differentiation, and immune response, and is implicated in the progression of fibrotic diseases and cancer. Extracellular activation of TGF-β1 from its latent form provides spatiotemporal control over TGF-β1 signaling, but the current understanding of TGF-β1 activation does not emphasize cross talk between activators. Plasmin (PLS) and thrombospondin-1 (TSP1) have been studied individually as activators of TGF-β1, and in this work we used a systems-level approach with mathematical modeling and in vitro experiments to study the interplay between PLS and TSP1 in TGF-β1 activation. Simulations and steady-state analysis predicted a switch-like bistable transition between two levels of active TGF-β1, with an inverse correlation between PLS and TSP1. In particular, the model predicted that increasing PLS breaks a TSP1-TGF-β1 positive feedback loop and causes an unexpected net decrease in TGF-β1 activation. To test these predictions in vitro, we treated rat hepatocytes and hepatic stellate cells with PLS, which caused proteolytic cleavage of TSP1 and decreased activation of TGF-β1. The TGF-β1 activation levels showed a cooperative dose response, and a test of hysteresis in the cocultured cells validated that TGF-β1 activation is bistable. We conclude that switch-like behavior arises from natural competition between two distinct modes of TGF-β1 a…
reaction: COPASI32
reaction: COPASI22
type: SBMLModel
reaction: COPASI44
reaction: COPASI28
reaction: COPASI18
curated: true
reaction: COPASI35
area units: area
species: COPASI2
species: COPASI10
species: COPASI3
reaction: COPASI14
length unit: length
reaction: COPASI43
reaction: COPASI31
reaction: COPASI21
reaction: COPASI27
name: Venkatraman2012 - Interplay between PLS and TSP1 in TGF-β1 activation
reaction: COPASI17
reaction: COPASI39
species: COPASI5
volume units: metaid_0000007
reaction: COPASI34
reaction: COPASI24
species: COPASI6
is described by: http://identifiers.org/pubmed/23009856
reaction: COPASI13
species: COPASI4
species: COPASI7
name: Constant flux (irreversible)
is: MODEL1303130000
reaction: COPASI30
reaction: COPASI20
reaction: COPASI42
parameter: COPASI12
reaction: COPASI26
reaction: COPASI16
reaction: COPASI38
reaction: COPASI33
reaction: COPASI23
reaction: COPASI29
reaction: COPASI19

http://identifiers.org/biomodels.db/BIOMD0000000447#dcc83352_2504_4af8_94b1_b93a4162003a
stoichiometry: 1.0
species: COPASI5
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#_48b96972_fed8_44a1_a474_5b701b834993
stoichiometry: 1.0
species: COPASI2
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#f69733fb_30c5_4180_ac75_714545284a35
stoichiometry: 1.0
species: COPASI7
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#ff96ef6e_97c6_4dda_9e49_e779597570fb
stoichiometry: 1.0
type: SpeciesReference

COPASI33
fast: false
reversible: false
name: reaction_21
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000447#ee084ecb_6dba_49b0_8ada_c22a35097ac7
stoichiometry: 1.0
species: COPASI5
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#_825f41ba_ed30_49b4_ac1d_9f94cc1341ed
stoichiometry: 1.0
type: SpeciesReference

COPASI23
type: Reaction
name: reaction_11
reversible: true
fast: false

http://identifiers.org/biomodels.db/BIOMD0000000447#_5627f12a_2e29_4e4f_8982_d7e21e8b7698
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#_22a76541_3273_42e6_93a8_97b75050696b
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#b1b6b14e_082c_4c60_8706_1285c7b0f343
stoichiometry: 1.0
species: COPASI7
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stoichiometry: 1.0
species: COPASI5
type: SpeciesReference

COPASI32
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reversible: false
name: reaction_20
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000447#_8ca9e164_6efa_4581_8061_4d3ebd6ad0ed
constant: true
value: 24.5
name: k5
type: Parameter

COPASI12
constant: true
value: 0.21
name: k9
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000447#_86f16bf7_5e25_4834_8042_4daab7b3f07f
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
name: PLS
type: Species

http://identifiers.org/biomodels.db/BIOMD0000000447#_51ddbc1c_c48c_4e78_b89c_0cce0993e441
name: substance
type: SBMLUnitsDef

COPASI7
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
name: PAI1
type: Species

COPASI43
fast: false
reversible: false
name: reaction_31
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000447#ffe16b91_7f2f_45d3_ac17_163588cfe96e
constant: true
value: 0.35
name: keff2
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000447#a1298187_36f5_432d_8647_1bb5b334d484
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#_24125435_c6eb_4337_a1bb_8d0e123171e8
stoichiometry: 1.0
species: COPASI10
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#c234fd6b_0050_444f_9fbb_23eecf11019a
stoichiometry: 1.0
type: SpeciesReference

COPASI31
fast: false
reversible: false
name: reaction_19
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000447#_73cf87cd_abd4_462e_adaf_361ec2fbae05
stoichiometry: 1.0
species: COPASI10
type: SpeciesReference

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stoichiometry: 1.0
type: SpeciesReference

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stoichiometry: 1.0
species: COPASI3
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http://identifiers.org/biomodels.db/BIOMD0000000447#_78612fee_a467_4cd5_b793_a5cb04ee3ff7
stoichiometry: 1.0
species: COPASI8
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#de5c374f_b7ab_4437_8592_32078816d010
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

COPASI11
constant: true
value: 17.5
name: k3
type: Parameter

COPASI6
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
name: TSP1
type: Species

http://identifiers.org/biomodels.db/BIOMD0000000447#f1575b4b_2d70_4eef_a975_92e5379d60b8
constant: true
value: 0.035
name: alpha2
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000447#_3d02e849_a997_4806_baff_4a156a3f3a6b
stoichiometry: 1.0
type: SpeciesReference

COPASI44
fast: false
reversible: false
name: reaction_32
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000447#_9f70fd74_e2b5_449e_a9fa_71e2569b863f
constant: true
size: 1.0
spatial dimensions: 3.0
name: compartment
type: Compartment

COPASI40
fast: false
reversible: false
name: reaction_29
type: Reaction

COPASI20
fast: false
reversible: false
name: reaction_8
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000447#_26f62096_01f5_4be2_a0a0_dc52c6b73d9e
stoichiometry: 1.0
type: SpeciesReference

COPASI30
fast: false
reversible: false
name: reaction_18
type: Reaction

COPASI10
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
name: PAI1:tcUPA
type: Species

http://identifiers.org/biomodels.db/BIOMD0000000447#_268d8e4c_5321_4c9e_a09c_c7a6779fc12a
constant: true
value: 0.35
name: kp1
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000447#_2509b92e_287b_4f90_802b_da84cd1e1732
stoichiometry: 1.0
type: SpeciesReference

COPASI9
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
name: A2M:PLS
type: Species

http://identifiers.org/biomodels.db/BIOMD0000000447#e3f00b5a_8362_40e4_bb86_22425b1ea36d
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#_898035ea_c987_4bbf_bc53_a75fdc5f77bc
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#a688b341_fdf2_4e63_ae27_12ea80cb1050
stoichiometry: 1.0
type: SpeciesReference

COPASI41
fast: false
reversible: false
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type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000447#_43717b00_7ab5_48bf_b345_ff0fc59d663b
constant: true
value: 0.0035
name: k_7
type: Parameter

COPASI8
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.005
initial amount: NaN
name: A2M
type: Species

http://identifiers.org/biomodels.db/BIOMD0000000447#_6052716e_58b5_4474_9571_41a83b429ab6
stoichiometry: 1.0
species: COPASI5
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#_4f711a9a_dedc_4ce9_9967_de6ac0aaceff
stoichiometry: 1.0
species: COPASI6
type: SpeciesReference

COPASI42
fast: false
reversible: false
name: reaction_27
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000447#_3b4a9125_3300_4db4_9125_8393e6652c71
constant: true
value: 0.035
name: k6
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000447#e33c7b05_3a67_4745_82b2_929fcf286f4e
stoichiometry: 1.0
species: COPASI8
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#_37e7d832_ea19_43ec_8582_12f21bbe3b12
constant: true
value: 1.4
name: keff3
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000447#_89e71fd1_07b5_4bad_8312_b833dc6682e4
stoichiometry: 1.0
species: COPASI5
type: SpeciesReference

COPASI3
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.001
initial amount: NaN
name: scUPA
type: Species

COPASI17
name: reaction_5
reversible: false
fast: false
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000447#cce6912a_e6d8_4aea_853b_8f61cfc19b03
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
name: tcUPA
type: Species

http://identifiers.org/biomodels.db/BIOMD0000000447#_6bbfe58d_f849_4273_a3d7_c6134a099ba8
stoichiometry: 1.0
species: COPASI4
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#_51737c2c_2fcd_4959_bbd1_773fc76b2fac
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#_724c7a09_17d5_4067_a853_b90424dae5f6
constant: true
value: 24.5
name: k2
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000447#_86020e68_afd9_43ca_be38_7b38720478c9
constant: true
value: 0.0105
name: k_5
type: Parameter

COPASI2
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.003
initial amount: NaN
name: PLG
type: Species

COPASI18
fast: false
reversible: false
name: reaction_6
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000447#e40ba9c3_19f4_4fb7_92ce_b65fe5141183
stoichiometry: 1.0
species: COPASI4
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#_217fa057_e2cd_4ae0_9bfd_b7594e92496f
stoichiometry: 1.0
species: COPASI3
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#_5cc06dc2_1650_4b53_b458_1088bcb292d5
stoichiometry: 1.0
species: COPASI7
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#ca897413_06b4_482e_9639_2b63f433b052
constant: true
value: 0.035
name: k1
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000447#_8c7616c3_8588_4ebe_ba5f_8dc5b2eacca5
stoichiometry: 1.0
species: COPASI6
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#_87ff29da_51a6_4cda_86de_77ce22f0c6ff
stoichiometry: 1.0
type: SpeciesReference

COPASI5
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
name: TGFb1
type: Species

COPASI19
fast: false
reversible: false
name: reaction_7
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000447#_6f696279_b35c_4ecd_9194_4ae276eceac2
constant: true
value: 0.35
name: k4
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000447#b96ace20_20a4_45e0_8c6b_7cdf6209b580
stoichiometry: 1.0
species: COPASI9
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#_76a4e914_975e_40a7_9e01_fd93a1acb031
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#_1fa593b2_28de_488e_a83c_6e867dda77d9
stoichiometry: 1.0
species: COPASI6
type: SpeciesReference

COPASI29
fast: false
reversible: false
name: reaction_17
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000447#_2017e444_44ae_4caa_bcaf_b40a80653370
stoichiometry: 1.0
species: COPASI4
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#d4e03b2f_190b_4263_a10a_25b9f53a147d
stoichiometry: 1.0
species: COPASI2
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#e91a6d02_4d96_44ba_84cd_1a31a7abf6eb
constant: true
value: 0.035
name: keff1
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000447#ebc6e47f_0dbd_4fff_ad69_1766379b7b7f
constant: true
value: 0.0175
name: u_pdeg
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000447#d1905a3e_19f8_4d3d_88f8_6a1afc3e8703
stoichiometry: 1.0
species: COPASI6
type: SpeciesReference

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stoichiometry: 1.0
species: COPASI4
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stoichiometry: 1.0
species: COPASI5
type: SpeciesReference

COPASI4
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.001
initial amount: NaN
name: LTGFb1
type: Species

http://identifiers.org/biomodels.db/BIOMD0000000447#f07ce333_49c6_4702_b0a1_ef63b2a62867
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#_4abed38f_3fa4_4bfe_9aed_2e6778ab55aa
stoichiometry: 1.0
species: COPASI7
type: SpeciesReference

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stoichiometry: 1.0
species: COPASI5
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stoichiometry: 1.0
species: COPASI9
type: SpeciesReference

COPASI13
fast: false
name: reaction_1
type: Reaction
reversible: false

COPASI27
fast: false
reversible: false
name: reaction_15
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000447#_8b3d856d_f7cf_4f49_82a1_240aa63d1b18
stoichiometry: 1.0
species: COPASI2
type: SpeciesReference

COPASI39
fast: false
reversible: false
name: reaction_28
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000447#_8b79f12d_e8a7_487b_b27f_57669b4fbd19
stoichiometry: 1.0
type: SpeciesReference

COPASI28
fast: false
reversible: false
name: reaction_16
type: Reaction

COPASI14
reversible: false
fast: false
type: Reaction
name: reaction_2

http://identifiers.org/biomodels.db/BIOMD0000000447#_34cd1d9d_af81_4b0b_b22f_af84a1e75979
stoichiometry: 1.0
species: COPASI5
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#e366d232_123f_46ed_8162_df5a6ddfca38
stoichiometry: 1.0
species: COPASI2
type: SpeciesReference

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stoichiometry: 1.0
species: COPASI5
type: SpeciesReference

COPASI38
fast: false
reversible: false
name: reaction_26
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000447#_88f6a8c2_ef65_4fb2_a3c9_5081be6e05db
stoichiometry: 1.0
type: SpeciesReference

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stoichiometry: 1.0
species: COPASI3
type: SpeciesReference

COPASI15
reversible: false
fast: false
type: Reaction
name: reaction_3

COPASI25
type: Reaction
name: reaction_13
reversible: true
fast: false

http://identifiers.org/biomodels.db/BIOMD0000000447#d2e5a1da_2025_47a5_8585_676172e9c83b
stoichiometry: 1.0
species: COPASI3
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#_60825958_0e29_4e2b_b0f5_481fa3c01ac5
stoichiometry: 1.0
species: COPASI8
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000447#_64ce7d96_34a4_49fb_8bbd_8b0858ae1c70
stoichiometry: 1.0
type: SpeciesReference

COPASI37
fast: false
reversible: false
name: reaction_25
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000447#_31f84bf3_77d5_44e9_b0c9_82130e6df4c7
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
name: PAI1:scUPA
type: Species

COPASI16
fast: false
reversible: false
type: Reaction
name: reaction_4

COPASI26
fast: false
reversible: false
name: reaction_14
type: Reaction