Thyroglobulin increases cell proliferation and suppresses Pax-8 in mesangial cells.
Thyroglobulin (Tg), has recently been identified as a transcriptional regulator of thyroid-restricted genes. The extrathyroidal expression of several of these genes (including the transcription factor Pax-8) together with the occurrence of specific Tg binding sites suggests a secondary role for Tg as a circulating hormone. In this study, we demonstrate using Northern analysis that Pax-8 is expressed in the mouse mesangial cell, and that its transcript levels are suppressed by Tg. These cells also express an asialoglycoprotein receptor, a receptor involved in Tg endocytosis in the thyroid, and a Tg transcript smaller than the 8.3-kb thyroidal form. Reverse transcriptase PCR showed that suppression of Pax-8 by Tg is correlated with reduced expression of bcl-2 apoptosis suppressor. Tg, but not triiodothyronine (T(3)) significantly increased MC proliferation above control as determined by DNA content of MC cultures. The effect of Tg on proliferation was not duplicated by either bovine serum albumin, gamma-globulins, lactoferrin, or the ASGPR-specific ligand,orosomucoid. These results suggest a possible endocrine role for Tg in regulating both Pax-8 related gene transcription and cell division in the mesangial cell.
Sellitti
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DF
Department of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. dsellitti@usuhs.mil
Suzuki
K
K
Doi
S Q
SQ
LaGranha
C
C
Machado
M
M
Matos
T
T
Kohn
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LD
D000818:Animals; D037263:Asialoglycoprotein Receptor; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013954:Thyroglobulin / Q000494:pharmacology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014284:Triiodothyronine / Q000494:pharmacology
D037263:Asialoglycoprotein Receptor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; C499496:Pax8 protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D014284:Triiodothyronine; D004247:DNA; D013954:Thyroglobulin