Disease relevance of Retnla

• Hypoxia caused robust HIMF induction in the lung, and HIMF has potent pulmonary vasoconstrictive, proliferative, and angiogenic properties [1].
• Finally, acute hyperglycemia leads to up-regulation of resistin and RELMalpha transcription in various adipose depots [2].
• ChaFFs may therefore be important effector or wound-repair molecules at the site of nematode infection, with potential regulatory roles for Ym1 and Fizz1 in the draining lymph nodes [3].
• However, the effects of HIMF on cell adhesion molecules involved in lung inflammation remain largely unknown [4].

High impact information on Retnla

• We also found that ICOS was not required for the differentiation of alternatively activated macrophages (AAMPhi) that express Ym1 and Fizz1 [5].
• RELMalpha is a secreted protein that has a restricted tissue distribution with highest levels in adipose tissue [6].
• In addition, RELMalpha is able to form heterooligomers with resistin but not RELMbeta [7].
• Here we demonstrate that RELMalpha inhibits the differentiation of 3T3-L1 preadipocytes into adipocytes [7].
• IRS-1 phosphorylation and glucose transport stimulated by insulin in mature adipocytes were also unaffected by RELMalpha [7].

Biological context of Retnla

• Treatment with HIMF resulted in a significant reduction of apoptosis in cultured embryonic lung, thus revealing a previously unknown function of HIMF [1].
• Since RELMalpha is expressed by adipose tissue and it is a secreted factor, our findings suggest that RELMalpha may be involved in the control of the adipogenesis as well as in the process of muscle differentiation [7].
• Resistin and RELM-alpha gene expression in white adipose tissue of lactating mice [8].
• However, RELM-alpha mRNA fell by approximately 40% in early lactation and there was a parallel fall in the leptin mRNA level proportional to the loss of fat mass [8].
• HIMF increased pulmonary arterial pressure and vascular resistance more potently than either endothelin-1 or angiotensin II [9].

Anatomical context of Retnla

• From embryonic day (E)16 to postnatal day (P)28, HIMF was strongly expressed in the cytoplasm of bronchial epithelial cells, type II cells, endothelial cells, and primitive mesenchymal cells [1].
• In addition to expression of ChaFFs in the tissues, Ym1 and Fizz1 expression was observed in the lymph nodes [3].
• Resistin and RELM-alpha mRNAs were both detectable in gonadal, subcutaneous, and mammary gland fat; mRNA level was highest in gonadal fat and lowest in mammary tissue [8].
• RELM-alpha decreased gallbladder optimal tension, but did not alter responses to neurotransmitters [10].
• However, whether HIMF exerts angiogenic effects through modulating endothelial cell function remains unknown [11].

Associations of Retnla with chemical compounds

• We note that RELM alpha lacks a cysteine residue, closest to the cleaved N terminus, that is present in resistin and RELM beta in multiple species [12].
• In comparison, Wy-14,643 reduced adiponectin transcript levels by 31% (P = 0.015) while BRL-35135 increased RELMalpha mRNA expression by 245% (P < 0.001) without effect on the other transcripts [13].
• The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (10 micromol/L) inhibited HIMF-activated Akt phosphorylation [9].
• Treatment of mouse aortic rings and SVEC 4-10 cells with LY294002, but not SB203580, PD098059 or U0126, abolished HIMF-induced vascular sprouting and angiogenic responses [11].
• In cultured mouse endothelial cell line SVEC 4-10, HIMF dose-dependently enhanced cell proliferation, in vitro migration and tubulogenesis, which was not attenuated by SU1498, a VEGFR2/Flk-1 receptor tyrosine kinase inhibitor [11].

Regulatory relationships of Retnla

• HIMF strongly activated Akt phosphorylation [9].

Other interactions of Retnla

• HIF-1alpha expression was temporally distinct from HIMF expression [1].
• Thus, HIMF and HIF-2alpha were temporally and spatially coexpressed in the developing lung [1].
• This study has examined the expression of the resistin and resistin-like molecule-alpha (RELM-alpha) genes in white adipose tissue of lactating mice [8].
• Thus, the PI3K/Akt pathway, at least in part, mediates the proliferative effect of HIMF [9].
• The activation status of macrophages was analyzed in this model of helminth infection by evaluating the expression of genetic markers of alternative activation, namely, Fizz1, Ym1, and Arg1 [14].

Analytical, diagnostic and therapeutic context of Retnla

• Results showed that HIMF is upregulated from Day 1 after pneumonectomy and peaking at Day 7 in the lung [15].
• Immunohistochemical staining and in situ hybridization showed that upregulated HIMF protein and mRNA are mainly distributed in airway epithelium, alveolar type II cells, and endothelial cells of the pulmonary vessels [15].
• We found that the expression of Arg-1, Fizz1, and NOS-2 in adherent bronchoalveolar lavage cells was highly up-regulated 3 days after silica administration but returned to control levels during the fibrotic stage of the disease (60 days) [16].
• Intravenous injection of HIMF also downregulated the expression of VEGFR2 in the lung [17].
• Houston-1, 90-615, and SA2 strains showed the same patterns in SDS-PAGE, but they differed from the patterns of B. henselae isolates URBHLLY8, URBHLIE9, Cat6, Fizz, and CAL-1 [18].

References