Modifiers & Inhibitors of Kidney Development in Culture

This table is part of the kidney development database.

Data from mutant animals (including transgenics) are listed in the mutant tables.

Note: [ - ] in table indicate 'no data', not 'no effect'.

Agent
Biochemical Effect
(or presumed effect)
Effect on Nephrogenesis
Effect on Ureteric Bud
References
Actinomycin D
-
blocked
-
Jainchill 1964
Activin A
-
none apparent
branching delayed & internodal gap increased
Ritvos et al 1995*
Angiopoietin I
signals via Tie-2
more nephrons become vascular
-
Kolatsi-Joannou 2001
Anti-BMP-7
prevents signalling by BMP-7
blocked
branching reduced
Vukiceric 1996
Sariola 1988
Anti-cadherin 6
prevents adhesion by cadherin-6
blocked after Pax 2 expression stage but before condensation
unaffected
Cho 1998
Anti-GD3
-
blocked
-
Sariola 1988
Anti-GDNF
prevents signalling by GDNF though c-Ret
-
inihbiton of growth & branching
Vega 1996
Anti-HGF
prevents signalling by HGF though c-Met
inhibition
inihbiton of growth & branching
Woolf 1995
Anti-L1
prevents L1-mediated cell adhesion
-
severe disruption of branching
Debiec 1998
Anti-laminin (alpha 6 integrin binding fragment)
prevents LN(A)-alpha6 integrin interaction
blocks polarization and subsequent development
-
Klein 1988
but see mutant table
Anti-laminin (nidogen binding fragment)
prevents LN-nidogen interaction
blocked
-
Ekblom 1994
Anti-midkine
blocks midkine action
inhibited
-
Vilar 2002
Anti-VEGF in animals
prevents VEGF action
nephrogenic areas diminished; little blood
-
Kitamoto 1997
Antisense BMP-7
blocks BMP-7 expression
blocked; fewer condensates etc (same with spinal cord induction)
reduced growth & branching
Vukiceric 1996
Antisense IGFI-R
blocks IGFI-R expression
reduced number of nephrons
reduced growth & branching
Lui 1993
Antisense MMP-2
blocks MMP-2 expression
-
reduced growth & branching
Kanwar 1999a
Antisense MT-1-MMP
blocks MT-1-MMP expression
-
reduced growth & branching
Kanwar 1999a
Antisense NGF-R
blocks p75-NGRF expression
blocks neprhogenesis
-
Sariola 1991
Antisense Pax2
blocks Pax2 expression
blocks nephrogenesis
-
-
Antisense mTim
blocks mTim expression
-
branching disrupted
Li 2000
Antisense TIMP-2
blocks TIMP-2 expression
-
explants larger
Kanwar 1999a
Antisense TIN-Ag
blocks tubulointerstitial nephritis antigen exprn
distal pole of S shaped tubule lost; glom OK
branching disrupted at high concs
Kanwar 1999b
BMP-2
-
-
reduction in branching
Gupta 1999
BMP-7
-
enhanced differentiation

increases survical of isolated MM
stimulates branching at low doses, inhibits at high doses
Vukiceric 1996
Gupta 1999
Dudley 1999
Caspase inhibitor
inhibits aopotosis
inhibits neprhogenesis
reduces branching
Araki 1999
Chlorate
prevents synthesis of sulphated GAGs
reduced number; mature normally
growth & branching blocked; growth can be rescued by HGF; branch initiation by PMA
Davies 1995b
Micrograph available
Chondroitinase & hepartinase combined
degradation of HSPG/CSPG
reduced number; mature normally
growth & branching blocked
Davies 1995b
Chondroitin sulphate
?
transfilter induction blocked
-
Ekblom 1978
Dextran sulphate
?
transfilter induction blocked
-
Ekblom 1978
DON
inhibiton of glycosylation
blocked
-
Ekblom 1979
EGF
signals through EGFR
promotes survival of stromal cells in isolated MM (incl ^BF2)
-
Ekblom 1979
Godin 1998
FGF-7
signals through FGFR-2
more neprhons
promotion of growth & branching but buds not well differentiated from tips
Qiao 1999 & 2001
FGF-10
signals through FGFR
-
promotion of growth & branching
Qiao 1999 & 2001
GDNF
signals through c-RET
-
promotion of growth & branching
Vega 1996
Sainio 1997
Heparin
?
transfilter induction blocked
-
Ekblom 1978
H-89
inhibits PKA
-
stimulates branching
Gupta 1999
Lactate
?
reduced nephrogenesis
-
Lovtrup-Rein 1978
LIF
?
nephrogenesis blocked at condensation
none
Bard 1991
Lithium ions
? modulation of second messengers
induces early stages of nephrogenesis in uninduced mesenchyme
-
Davies 1995a
NT-3
-
neural differentiation promoted
-
Karavanov 1995
Okadaic acid 10nM
2nd messenger modulation (esp phosphatases)
nephrogenesis inhibited & growth blocked
growth blocked; may be a secondary effect
Svennilson 1995
PD98059
blocks MAP Kinase activation
-
branching blocked
Fisher 2001
Pleiotrophin
-
-
drives branching
Sakurai 2001
Polycystin PKD rpt peptides
? competitive inhibition of PKD-ligand binding
nephrogenesis reduced
branch pattern altered & reduced; asymmetry
Van Adelsberg 1999
Retinol, ATRA, 9-cis-RA
up-regulates c-Ret expression
increased number of neprhons; 3-6 times
more growth & branching
Vilar 1996
Moreau 1998
sFRP-1
modulates Wnt siganlling
nephrogenesis inhibited
branching inhibited
Yoshino 2001
sFRP-2
modulates Wnt siganlling
antagonizes sFRP-1
-
Yoshino 2001
TGF-beta
-
-
branching altered
Ritvos 1995
TIMP-1
inhibits MMP-9
-
branching inhibited
LeLongt 1997
Tunicamycin
inhibition of glycosylation
transfilter induction blocked
-
Ekblom 1979b
Wt1 siRNA
inhibition of WT1 expression
nephron differention blocked
apparently nil
Davies 2004
Agent
Biochemical Effect
(or presumed effect)
Effect on Nephrogenesis
Effect on Ureteric Bud
References

* Notes: Activin A; images available from http://sdb.bio.purdue.edu/SDBShowTell/GilbertActivin.html


Date of last revision: January 2006
Comments about the database are always welcome.
Email: Jamie.Davies@ed.ac.uk