PMID- 11708867
OWN - NLM
STAT- MEDLINE
DCOM- 20020108
LR  - 20181130
IS  - 1096-7192 (Print)
IS  - 1096-7192 (Linking)
VI  - 74
IP  - 3
DP  - 2001 Nov
TI  - Limited cooperation between peroxisome proliferator-activated receptors and 
      retinoid X receptor agonists in sebocyte growth and development.
PG  - 362-9
AB  - We have found that sebaceous epithelial cell (sebocyte) differentiation is 
      induced by cognate ligand-agonists of either peroxisome proliferator-activated 
      receptors (PPARs) or retinoid X receptors (RXRs). In this study, we tested the 
      hypothesis that PPAR-RXR cooperation is used in sebocytes as was reported to 
      occur in gene transfection systems and liposarcoma cells through PPAR-RXR 
      heterodimerization. PPAR agonists at maximally effective concentrations were 
      tested in combination with a specific RXR agonist (the rexinoid CD2809) at doses 
      ranging from submaximal to maximal in a primary rat preputial cell monolayer 
      culture system. We evaluated ligand-agonists of PPARalpha (WY-14643 = WY), 
      PPARgamma (troglitazone = TRO), and PPARdelta,alpha (carbaprostacyclin = cPGI2). 
      Cell differentiation was determined by analysis of lipid staining and 
      proliferation by cell counting. The RXR agonist induced a more diffuse and 
      granular pattern of lipid staining throughout colonies than did PPAR agonists. 
      The PPAR ligands WY, TRO, and cPGI2 induced 37, 35, and 59% lipid-forming 
      colonies (LFCs), respectively (P < 0.05 vs controls, which averaged 19%). 
      Low-dose rexinoid (10(-8) M) alone exerted no significant effect but amplified 
      the effect of cPGI2 (P < 0.05). Middose rexinoid (10(-7) M), which alone induced 
      about 40% LFCs, had an additive effect on differentiation with WY, TRO, and cPGI2 
      (71, 48, and 83% LFCs respectively, P < 0.05 vs each agonist alone). 
      Proliferation was enhanced significantly by either rexinoid or cPGI2, but there 
      was no change in growth when the two were added together. The greater 
      effectiveness of cPGI2 than the other PPAR agonists may be explained by the 
      predominance of PPARdelta gene expression in cultured sebocytes, as demonstrated 
      by RNase protection assay. These studies demonstrate that a submaximal dose of 
      RXR agonist augmented the stimulation of sebocyte differentiation by PPAR 
      agonists, as expected from PPAR-RXR heterodimerization. However, the evidence for 
      PPAR-RXR cooperativity is limited. The pattern of lipid staining is compatible 
      with an independent effect of rexinoid on sebocyte differentiation. Furthermore, 
      since there is no enhancement of the growth-promoting effects of RXR agonist and 
      cPGI2 when they are combined, this effect also does not appear to be mediated by 
      PPAR-RXR interaction.
CI  - Copyright 2001 Academic Press.
FAU - Kim, M J
AU  - Kim MJ
AD  - Department of Pediatrics, University of Chicago Pritzker School of Medicine, 
      Chicago, IL 60637, USA.
FAU - Deplewski, D
AU  - Deplewski D
FAU - Ciletti, N
AU  - Ciletti N
FAU - Michel, S
AU  - Michel S
FAU - Reichert, U
AU  - Reichert U
FAU - Rosenfield, R L
AU  - Rosenfield RL
LA  - eng
GR  - HD-06308/HD/NICHD NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Genet Metab
JT  - Molecular genetics and metabolism
JID - 9805456
RN  - 0 (CD 2809)
RN  - 0 (Chromans)
RN  - 0 (Protein Isoforms)
RN  - 0 (Pyrimidines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Thiazoles)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Transcription Factors)
RN  - 69552-46-1 (carboprostacyclin)
RN  - 86C4MRT55A (pirinixic acid)
RN  - DCR9Z582X0 (Epoprostenol)
RN  - I66ZZ0ZN0E (Troglitazone)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/*drug effects
MH  - Cell Division/*drug effects
MH  - Cells, Cultured
MH  - Chromans/pharmacology
MH  - Drug Synergism
MH  - Epoprostenol/*analogs & derivatives/pharmacology
MH  - Male
MH  - Protein Isoforms/agonists/genetics
MH  - Pyrimidines/pharmacology
MH  - RNA, Messenger/drug effects/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Calcitriol
MH  - Receptors, Cytoplasmic and Nuclear/*agonists
MH  - Receptors, Retinoic Acid/*agonists/genetics
MH  - Retinoid X Receptors
MH  - Sebaceous Glands/cytology/*drug effects
MH  - Stem Cells/drug effects
MH  - Thiazoles/pharmacology
MH  - *Thiazolidinediones
MH  - Transcription Factors/*agonists/genetics/pharmacology
MH  - Troglitazone
EDAT- 2001/11/16 10:00
MHDA- 2002/01/10 10:01
CRDT- 2001/11/16 10:00
PHST- 2001/11/16 10:00 [pubmed]
PHST- 2002/01/10 10:01 [medline]
PHST- 2001/11/16 10:00 [entrez]
AID - S1096-7192(01)93242-1 [pii]
AID - 10.1006/mgme.2001.3242 [doi]
PST - ppublish
SO  - Mol Genet Metab. 2001 Nov;74(3):362-9. doi: 10.1006/mgme.2001.3242.