UGRP1, a uteroglobin/Clara cell secretory protein-related protein, is a novel lung-enriched downstream target gene for the T/EBP/NKX2.1 Homeodomain transcription factor

T. Niimi, C. L. Keck-Waggoner, N. C. Popescu, Y. Zhou, Roy C Levitt, S. Kimura

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

A novel gene that is down-regulated in lungs of T/ebp/Nkx2.1-null mouse embryos has been identified using a suppressive-subtractive hybridization method. The gene product is a secreted protein, forms a homodimer, and exhibits an amino acid sequence similar to that seen in the uteroglobin/Clara cell secretory protein family of proteins. This gene, designated Ugrp1 (uteroglobin-related protein 1), consists of three exons and two introns and produces three transcripts by alternative splicing. The Ugrp1 gene was localized by fluorescence in situ hybridization to mouse chromosome 18 at region 18C-D;this region is homologous with human 5q31-34, where one of the asthma susceptibility genes has been assigned. UGRP1 mRNA is predominantly expressed in the lung, with low levels of expression in the thyroid. Expression in the lung is detectable as early as embryonic day 12.5 and increases markedly by embryonic day 16.5. In T/ebp/Nkx2.1-null embryo lungs, UGRP1 expression was significantly reduced as assessed by RT-PCR analysis. Cotransfection assays using a T/EBP/NKX2.1 expression construct with Ugrp1 promoter-luciferase reporter constructs confirmed that T/EBP/NKX2.1 regulates Ugrp1 gene activity at the transcriptional level. Thus, Ugrp1 is a downstream target gene for the T/EBP/NKX2.1 homeodomain transcription factor. Changes in UGRP1 mRNA levels in lungs from antigen-sensitized mice suggest the possible involvement of UGRP1 in inflammation.

Original languageEnglish
Pages (from-to)2021-2036
Number of pages16
JournalMolecular Endocrinology
Volume15
Issue number11
DOIs
StatePublished - Nov 12 2001
Externally publishedYes

Fingerprint

Uteroglobin
Transcription Factors
Lung
Genes
Proteins
Embryonic Structures
Chromosomes, Human, Pair 18
Messenger RNA
Alternative Splicing
Luciferases
Fluorescence In Situ Hybridization
Introns
Amino Acid Sequence
Exons
Thyroid Gland
Asthma
Inflammation
Antigens
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

UGRP1, a uteroglobin/Clara cell secretory protein-related protein, is a novel lung-enriched downstream target gene for the T/EBP/NKX2.1 Homeodomain transcription factor. / Niimi, T.; Keck-Waggoner, C. L.; Popescu, N. C.; Zhou, Y.; Levitt, Roy C; Kimura, S.

In: Molecular Endocrinology, Vol. 15, No. 11, 12.11.2001, p. 2021-2036.

Research output: Contribution to journalArticle

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abstract = "A novel gene that is down-regulated in lungs of T/ebp/Nkx2.1-null mouse embryos has been identified using a suppressive-subtractive hybridization method. The gene product is a secreted protein, forms a homodimer, and exhibits an amino acid sequence similar to that seen in the uteroglobin/Clara cell secretory protein family of proteins. This gene, designated Ugrp1 (uteroglobin-related protein 1), consists of three exons and two introns and produces three transcripts by alternative splicing. The Ugrp1 gene was localized by fluorescence in situ hybridization to mouse chromosome 18 at region 18C-D;this region is homologous with human 5q31-34, where one of the asthma susceptibility genes has been assigned. UGRP1 mRNA is predominantly expressed in the lung, with low levels of expression in the thyroid. Expression in the lung is detectable as early as embryonic day 12.5 and increases markedly by embryonic day 16.5. In T/ebp/Nkx2.1-null embryo lungs, UGRP1 expression was significantly reduced as assessed by RT-PCR analysis. Cotransfection assays using a T/EBP/NKX2.1 expression construct with Ugrp1 promoter-luciferase reporter constructs confirmed that T/EBP/NKX2.1 regulates Ugrp1 gene activity at the transcriptional level. Thus, Ugrp1 is a downstream target gene for the T/EBP/NKX2.1 homeodomain transcription factor. Changes in UGRP1 mRNA levels in lungs from antigen-sensitized mice suggest the possible involvement of UGRP1 in inflammation.",
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