Hypoxic regulation of β-1,3-glucuronyltransferase 1 expression in nucleus pulposus cells of the rat intervertebral disc: role of hypoxia-inducible factor proteins.
Hypoxic regulation of β-1,3-glucuronyltransferase 1 expression in nucleus pulposus cells of the rat intervertebral disc: role of hypoxia-inducible factor proteins.
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DOI：
10.1002/art.30342
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发表时间：
2011-07
影响因子：
--
通讯作者：
Risbud, Makarand V.
中科院分区：
文献类型：
--
作者：
Gogate, Shilpa S.;Nasser, Rena;Shapiro, Irving M.;Risbud, Makarand V.
The goal of the investigation was to study if hypoxia and HIF proteins regulate expression of GlcAT-I, a key enzyme in GAG synthesis in nucleus pulposus (NP) cells. QRT-PCR and Western blot were used to measure GlcAT-I expression. Transfections were performed to determine the effect of HIF-1/-2 on GlcAT-I promoter activity. In hypoxia there was an increase in GlcAT-I expression; a significant increase in promoter activity was seen in both NP and N1511 chondrocytes. We investigated if HIF controlled GlcAT-I expression. Suppression of HIF-1α and HIF-2α induced GlcAT-I promoter activity and expression only in NP cells. While, GlcAT-I promoter activity was suppressed by co-expression of both CA-HIF-1α and CA-HIF-2α only in NP cells suggesting a cell type specific regulation. Site directed mutagenesis and deletion constructs were used to further confirm the suppressive role of HIFs on GlcAT-I promoter function in NP cells. Although it was evident that interaction of HIF with HRE results in suppression of basal promoter activity, it was not necessary for transcriptional suppression. This result suggested both a direct and an indirect mode of regulation possibly through recruitment of a HIF-dependent repressor. Finally we show that hypoxic expression of GlcAT-I was also partially dependent on MAPK signaling. Results of these studies demonstrate that hypoxia regulates GlcAT-I expression through a signaling network comprising both an activator and suppressor molecules and that this regulation is unique to NP cells.
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影响因子：
4.8
作者：
Tsai, Tsung-Ting;Danielson, Keith G.;Risbud, Makarand V.
通讯作者：
Risbud, Makarand V.
DOI：
10.1359/jbmr.091202
发表时间：
2010-05
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Hiyama A;Gogate SS;Gajghate S;Mochida J;Shapiro IM;Risbud MV
通讯作者：
Risbud MV
影响因子：
2.9
作者：
Robinson, MJ;Harkins, PC;Goldsmith, EJ
通讯作者：
Goldsmith, EJ
DOI：
10.3109/17453676908989540
发表时间：
1969-01-01
期刊：
ACTA ORTHOPAEDICA SCANDINAVICA
影响因子：
--
作者：
HASSLER, O
通讯作者：
HASSLER, O
影响因子：
--
作者：
Agrawal, Amit;Gajghate, Sachin;Risbud, Makarand V.
通讯作者：
Risbud, Makarand V.