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Hypoxia inducible factor-1 mediates expression of miR-322: potential role in proliferation and migration of pulmonary arterial smooth muscle cells.

Zeng Y, Liu H, Kang K, Wang Z, Hui G, Zhang X, Zhong J, Peng W, Ramchandran R, Raj JU, Gou D - Sci Rep (2015)

Bottom Line: We demonstrated that HIF-1α, but not HIF-2α, transcriptionally upregulates the expression of miR-322 in hypoxia.Furthermore, miR-322 facilitated the accumulation of HIF-1α in the nucleus and promoted hypoxia-induced cell proliferation and migration.Direct targeting BMPR1a and smad5 by miR-322 was demonstrated in PASMCs suggesting that downregulation of BMP-Smad signaling pathway may be mediating the hypoxia-induced PASMC proliferation and migration.

View Article: PubMed Central - PubMed

Affiliation: 1] Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen Key Laboratory of Marine Bioresourse and Eco-environmental Science, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China [2] Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, 518060, China.

ABSTRACT
There is growing evidence that microRNAs play important roles in cellular responses to hypoxia and in pulmonary hypertensive vascular remodeling, but the exact molecular mechanisms involved are not fully elucidated. In this study, we identified miR-322 as one of the microRNAs induced in lungs of chronically hypoxic mice and rats. The expression of miR-322 was also upregulated in primary cultured rat pulmonary arterial smooth muscle cells (PASMC) in response to hypoxia. We demonstrated that HIF-1α, but not HIF-2α, transcriptionally upregulates the expression of miR-322 in hypoxia. Furthermore, miR-322 facilitated the accumulation of HIF-1α in the nucleus and promoted hypoxia-induced cell proliferation and migration. Direct targeting BMPR1a and smad5 by miR-322 was demonstrated in PASMCs suggesting that downregulation of BMP-Smad signaling pathway may be mediating the hypoxia-induced PASMC proliferation and migration. Our study implicates miR-322 in the hypoxic proliferative response of PASMCs suggesting that it may be playing a role in pulmonary vascular remodeling associated with pulmonary hypertension.

No MeSH data available.


Related in: MedlinePlus

miR-322 promotes migration of PASMCs.(a, c) Representative images of wound-healing assay showing migration of rat PASMC either with miR-322 overexpression or knockdown. (b, d) Bar chart showing relative decreased wound width after 24 h. Data are shown as mean ± SD. *p < 0.05 compared to miR-Con or anti-Con.
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f6: miR-322 promotes migration of PASMCs.(a, c) Representative images of wound-healing assay showing migration of rat PASMC either with miR-322 overexpression or knockdown. (b, d) Bar chart showing relative decreased wound width after 24 h. Data are shown as mean ± SD. *p < 0.05 compared to miR-Con or anti-Con.

Mentions: Cell migration was assessed through a wound-healing assay. As shown in Fig. 6, the decrease in the width of the scratched wound was larger (~ 60%) in miR-322 transfected cells than in control cells after 24 h (Fig. 6a,b), and knockdown of miR-322 led to a slower decrease in wound healing compared with anti-Con transfection (~ 40%) after 24 h (Fig. 6c,d). Taken together these data demonstrate that hypoxia-induced miR-322 can promote migration of PASMCs.


Hypoxia inducible factor-1 mediates expression of miR-322: potential role in proliferation and migration of pulmonary arterial smooth muscle cells.

Zeng Y, Liu H, Kang K, Wang Z, Hui G, Zhang X, Zhong J, Peng W, Ramchandran R, Raj JU, Gou D - Sci Rep (2015)

miR-322 promotes migration of PASMCs.(a, c) Representative images of wound-healing assay showing migration of rat PASMC either with miR-322 overexpression or knockdown. (b, d) Bar chart showing relative decreased wound width after 24 h. Data are shown as mean ± SD. *p < 0.05 compared to miR-Con or anti-Con.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4499844&req=5

f6: miR-322 promotes migration of PASMCs.(a, c) Representative images of wound-healing assay showing migration of rat PASMC either with miR-322 overexpression or knockdown. (b, d) Bar chart showing relative decreased wound width after 24 h. Data are shown as mean ± SD. *p < 0.05 compared to miR-Con or anti-Con.
Mentions: Cell migration was assessed through a wound-healing assay. As shown in Fig. 6, the decrease in the width of the scratched wound was larger (~ 60%) in miR-322 transfected cells than in control cells after 24 h (Fig. 6a,b), and knockdown of miR-322 led to a slower decrease in wound healing compared with anti-Con transfection (~ 40%) after 24 h (Fig. 6c,d). Taken together these data demonstrate that hypoxia-induced miR-322 can promote migration of PASMCs.

Bottom Line: We demonstrated that HIF-1α, but not HIF-2α, transcriptionally upregulates the expression of miR-322 in hypoxia.Furthermore, miR-322 facilitated the accumulation of HIF-1α in the nucleus and promoted hypoxia-induced cell proliferation and migration.Direct targeting BMPR1a and smad5 by miR-322 was demonstrated in PASMCs suggesting that downregulation of BMP-Smad signaling pathway may be mediating the hypoxia-induced PASMC proliferation and migration.

View Article: PubMed Central - PubMed

Affiliation: 1] Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen Key Laboratory of Marine Bioresourse and Eco-environmental Science, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China [2] Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, 518060, China.

ABSTRACT
There is growing evidence that microRNAs play important roles in cellular responses to hypoxia and in pulmonary hypertensive vascular remodeling, but the exact molecular mechanisms involved are not fully elucidated. In this study, we identified miR-322 as one of the microRNAs induced in lungs of chronically hypoxic mice and rats. The expression of miR-322 was also upregulated in primary cultured rat pulmonary arterial smooth muscle cells (PASMC) in response to hypoxia. We demonstrated that HIF-1α, but not HIF-2α, transcriptionally upregulates the expression of miR-322 in hypoxia. Furthermore, miR-322 facilitated the accumulation of HIF-1α in the nucleus and promoted hypoxia-induced cell proliferation and migration. Direct targeting BMPR1a and smad5 by miR-322 was demonstrated in PASMCs suggesting that downregulation of BMP-Smad signaling pathway may be mediating the hypoxia-induced PASMC proliferation and migration. Our study implicates miR-322 in the hypoxic proliferative response of PASMCs suggesting that it may be playing a role in pulmonary vascular remodeling associated with pulmonary hypertension.

No MeSH data available.


Related in: MedlinePlus