Regulation of the murine α2(I) collagen promoter by retinoic acid and retinoid X receptors

Lan Wang; Lynda Rennie Tankersley; Mei Tang; James J. Potter; Esteban Mezey

doi:10.1016/S0003-9861(02)00058-9

Regulation of the murine α₂(I) collagen promoter by retinoic acid and retinoid X receptors

Lan Wang, Lynda Rennie Tankersley, Mei Tang, James J. Potter, Esteban Mezey

School of Medicine

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

Retinoic acid decreases collagen production by hepatic stellate cells. This study investigated the effects of retinoic acid receptor β(RARβ) and retinoid X receptor α(RXRα) on the regulation of the α₂(I) collagen promoter. Retinoic acid and the RARβ and RXRα expression vectors suppressed the promoter in transfected stellate cells with maximal suppression obtained when combined. Mutation of the retinoic acid response element (RARE) at -879 to -874 (site 1) enhanced promoter activity and diminished but did not eliminate the suppression by RARβ and RXRα. Mutation of another RARE site (site 2), at -930 to -911, resulted in low activity that was inhibited by retinoic acid. Mutation of the AP-2-binding site enhanced promoter activity that was inhibited by retinoic acid. This study shows that the suppressive effect of retinoic acid on the promoter is maximal with a combination of RARβ and RXRα and occurs at more than one RARE site. The effect of retinoic acid is not mediated by AP-2.

Original language	English (US)
Pages (from-to)	262-270
Number of pages	9
Journal	Archives of Biochemistry and Biophysics
Volume	401
Issue number	2
DOIs	https://doi.org/10.1016/S0003-9861(02)00058-9
State	Published - May 15 2002

Keywords

AP-2
Acetaldehyde
Retinoic acid
Retinoic acid receptor
Retinoid X receptor
Stellate cells
Type I collagen promoter

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology

Access to Document

10.1016/S0003-9861(02)00058-9

Cite this

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title = "Regulation of the murine α2(I) collagen promoter by retinoic acid and retinoid X receptors",

abstract = "Retinoic acid decreases collagen production by hepatic stellate cells. This study investigated the effects of retinoic acid receptor β(RARβ) and retinoid X receptor α(RXRα) on the regulation of the α2(I) collagen promoter. Retinoic acid and the RARβ and RXRα expression vectors suppressed the promoter in transfected stellate cells with maximal suppression obtained when combined. Mutation of the retinoic acid response element (RARE) at -879 to -874 (site 1) enhanced promoter activity and diminished but did not eliminate the suppression by RARβ and RXRα. Mutation of another RARE site (site 2), at -930 to -911, resulted in low activity that was inhibited by retinoic acid. Mutation of the AP-2-binding site enhanced promoter activity that was inhibited by retinoic acid. This study shows that the suppressive effect of retinoic acid on the promoter is maximal with a combination of RARβ and RXRα and occurs at more than one RARE site. The effect of retinoic acid is not mediated by AP-2.",

keywords = "AP-2, Acetaldehyde, Retinoic acid, Retinoic acid receptor, Retinoid X receptor, Stellate cells, Type I collagen promoter",

author = "Lan Wang and {Rennie Tankersley}, Lynda and Mei Tang and Potter, {James J.} and Esteban Mezey",

note = "Funding Information: This work was supported by Grants AA00626 and K01-AA00323 from the United States Public Health Service. L.W. and M.T. were postdoctoral fellows on National Research Service Award 2 T32 AA07467 from the National Institute of Alcohol Abuse and Alcoholism (NIH).",

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AU - Wang, Lan

AU - Rennie Tankersley, Lynda

AU - Tang, Mei

AU - Potter, James J.

AU - Mezey, Esteban

N1 - Funding Information: This work was supported by Grants AA00626 and K01-AA00323 from the United States Public Health Service. L.W. and M.T. were postdoctoral fellows on National Research Service Award 2 T32 AA07467 from the National Institute of Alcohol Abuse and Alcoholism (NIH).

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N2 - Retinoic acid decreases collagen production by hepatic stellate cells. This study investigated the effects of retinoic acid receptor β(RARβ) and retinoid X receptor α(RXRα) on the regulation of the α2(I) collagen promoter. Retinoic acid and the RARβ and RXRα expression vectors suppressed the promoter in transfected stellate cells with maximal suppression obtained when combined. Mutation of the retinoic acid response element (RARE) at -879 to -874 (site 1) enhanced promoter activity and diminished but did not eliminate the suppression by RARβ and RXRα. Mutation of another RARE site (site 2), at -930 to -911, resulted in low activity that was inhibited by retinoic acid. Mutation of the AP-2-binding site enhanced promoter activity that was inhibited by retinoic acid. This study shows that the suppressive effect of retinoic acid on the promoter is maximal with a combination of RARβ and RXRα and occurs at more than one RARE site. The effect of retinoic acid is not mediated by AP-2.

AB - Retinoic acid decreases collagen production by hepatic stellate cells. This study investigated the effects of retinoic acid receptor β(RARβ) and retinoid X receptor α(RXRα) on the regulation of the α2(I) collagen promoter. Retinoic acid and the RARβ and RXRα expression vectors suppressed the promoter in transfected stellate cells with maximal suppression obtained when combined. Mutation of the retinoic acid response element (RARE) at -879 to -874 (site 1) enhanced promoter activity and diminished but did not eliminate the suppression by RARβ and RXRα. Mutation of another RARE site (site 2), at -930 to -911, resulted in low activity that was inhibited by retinoic acid. Mutation of the AP-2-binding site enhanced promoter activity that was inhibited by retinoic acid. This study shows that the suppressive effect of retinoic acid on the promoter is maximal with a combination of RARβ and RXRα and occurs at more than one RARE site. The effect of retinoic acid is not mediated by AP-2.

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KW - Stellate cells

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