INT295087

Context Info Confidence 0.67 First Reported 2010 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 1 Total Number 14 Disease Relevance 1.89 Pain Relevance 0

transport (Slc20a2) plasma membrane (Slc20a2)

Anatomy Link Frequency liver 8 embryos 2 HeLa 1 Slc20a2 (Mus musculus)

Pain Link Frequency Relevance Heat Osteoarthritis 14 20.48 cva 28 5.00 anesthesia 14 5.00 isoflurane 14 5.00

Disease Link Frequency Relevance Heat Apoptosis 196 99.00 Embryonic Lethality 112 90.96 Osteoporosis 70 75.92 Sprains And Strains 14 73.00 Hematological Disease 28 72.96 Anaemia 196 71.84 Death 70 62.56 Leukemia 14 57.96 Congenital Anomalies 56 43.76 Calcification 84 30.16

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

In PiT1-null fetal livers we show that PiT2 is overexpressed but that this overexpression does not compensate for the loss of PiT1.

Gene_expression (overexpressed) of PiT2 in livers

1) Confidence 0.67 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2818845 Disease Relevance 0 Pain Relevance 0

Our results show that, although PiT2 expression is unchanged, PiT1 is highly (3.5-fold) induced within 2 h following partial hepatectomy (Fig. 7F) indicating that PiT1 is likely to be essential during the early stage of compensatory liver growth.

Gene_expression (expression) of PiT2 in liver

2) Confidence 0.67 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2818845 Disease Relevance 0.06 Pain Relevance 0

The over-expression of PiT2 in PiT1-deficient embryos suggests that PiT2 may compensate for the lack of PiT1 up until this stage.

Gene_expression (expression) of PiT2 in embryos

3) Confidence 0.67 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2818845 Disease Relevance 0.32 Pain Relevance 0

However, decreased proliferation and increased apoptosis of PiT1-deficient fetal livers arise despite the over-expression of PiT2 in the liver, demonstrating that PiT2 can not take over the function of PiT1 in the liver, and argues for distinct temporal or tissue-specific roles for PiT1 and PiT2.

Gene_expression (over) of PiT2 in liver associated with apoptosis

4) Confidence 0.67 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2818845 Disease Relevance 0.28 Pain Relevance 0

Moreover, quantification of the relative expression of PiT1 and PiT2 in wild-type fetal and post-natal livers revealed that PiT1 expression was 3.4-fold higher in fetal livers and 1.7-fold lower in post natal livers than PiT2 (Fig. 7D), further illustrating the need for PiT1 during developmental liver growth.

Gene_expression (expression) of PiT2 in livers

5) Confidence 0.67 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2818845 Disease Relevance 0.11 Pain Relevance 0

We have shown that the proliferation rate of PiT1-null MEFs is decreased while the Na+-Pi transport activity remains unchanged, most probably due to the over-expression of PiT2 that is observed in PiT1-deficient MEFs.

Gene_expression (over-expression) of PiT2

6) Confidence 0.67 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2818845 Disease Relevance 0.06 Pain Relevance 0

Moreover, significant differences between PiT1 and PiT2 expression levels and ratios are observed among tissues [9], which suggests that these two transporters may have specific and non redundant roles in vivo.

Gene_expression (expression) of PiT2

7) Confidence 0.67 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2818845 Disease Relevance 0.19 Pain Relevance 0

We confirmed these results by quantifying the expression of PiT1 and PiT2 in fetal E12.5 and post-natal P15 wild-type livers by real-time RT-PCR.

Gene_expression (expression) of PiT2 in livers

8) Confidence 0.67 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2818845 Disease Relevance 0.19 Pain Relevance 0

Therefore it is tempting to speculate that as in MEFs, HepG2 and HeLa cells [9], a PiT2 overexpression in mutant livers could compensate for a loss of Na+-Pi transport activity (as it is shared by PiT1 and PiT2), but not for a loss of a PiT1-specific function such as the proliferation-related function of PiT1.

Gene_expression (overexpression) of PiT2 in HeLa

9) Confidence 0.67 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2818845 Disease Relevance 0 Pain Relevance 0

The level of PiT1 in the fetal liver was 4.4-fold higher than that in the post-natal liver, whereas fetal and post-natal PiT2 expression were similar (Fig. 7C).

Gene_expression (expression) of PiT2 in liver

10) Confidence 0.59 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2818845 Disease Relevance 0.12 Pain Relevance 0

5 E12.5 livers, the expression of PiT2 was 1.5-fold higher than in the wild-type livers (Fig. 7E), a value that is comparable to the increase found in the whole mutant embryo (Fig. 1F).

Gene_expression (expression) of PiT2 in livers

11) Confidence 0.59 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2818845 Disease Relevance 0 Pain Relevance 0

5 MEFs was abolished, this was associated with a 1.8-fold overexpression of PiT2 mRNA (Fig. 8C), which could account for the maintenance of normal Na+-Pi transport in PiT1-null MEFs.

Gene_expression (overexpression) of PiT2

12) Confidence 0.58 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2818845 Disease Relevance 0.06 Pain Relevance 0

5 embryos represented 6% of normal levels whereas PiT2 expression was increased, as was seen in PiT1neo/neo and PiT1?

Gene_expression (expression) of PiT2 in embryos

13) Confidence 0.58 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2818845 Disease Relevance 0.24 Pain Relevance 0

However, decreased proliferation and increased apoptosis of PiT1-deficient fetal livers arise despite the over-expression of PiT2 in the liver, demonstrating that PiT2 can not take over the function of PiT1 in the liver, and argues for distinct temporal or tissue-specific roles for PiT1 and PiT2.

Gene_expression (expression) of PiT2 in liver associated with apoptosis

14) Confidence 0.52 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2818845 Disease Relevance 0.28 Pain Relevance 0

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