Platelet-derived Growth Factor D, Tissue-specific Expression in the Eye, and a Key Role in Control of Lens Epithelial Cell Proliferation

Ray, Sugata; Gao, Chun; Wyatt, Keith; Fariss, Robert N.; Bundek, A.M.; Zelenka, Peggy S.; Wistow, Graeme

doi:10.1074/jbc.m413570200

Cited by 30 publications

(23 citation statements)

References 34 publications

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“…Neither of these two kinases have been implicated in preadipocyte survival responses. In any case, to more precisely implicate PDGFR, we immunodepleted the MacCM of PDGF by immunoprecipitation with PDGF antibody, an approach used by others (29). PDGF-immunodepleted MacCM was unable to stimulate tyrosine phosphorylation acutely and could no longer sustain preadipocytes subjected to serum withdrawal over the 6-h time period.…”

Section: Discussionmentioning

confidence: 99%

Preadipocyte apoptosis is prevented by macrophage-conditioned medium in a PDGF-dependent manner

Molgat

Gagnon²,

Sorisky³

2009

American Journal of Physiology-Cell Physiology

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Molgat AS, Gagnon A, Sorisky A. Preadipocyte apoptosis is prevented by macrophage-conditioned medium in a PDGF-dependent manner. Am J Physiol Cell Physiol 296: C757-C765, 2009. First published February 18, 2009 doi:10.1152/ajpcell.00617.2008.-Obesity is associated with macrophage accumulation and inflammation in adipose tissue. Macrophage-secreted factors have been reported to inhibit the differentiation of preadipocytes into adipocytes and to modulate adipogenic extracellular matrix gene expression. To enlarge our understanding of macrophages and the scope of their interactions with preadipocytes, we investigated their effect on preadipocyte survival. Acute exposure of 3T3-L1 preadipocytes to J774A.1 macrophage-conditioned medium (MacCM) stimulated platelet-derived growth factor receptor (PDGFR) tyrosine phosphorylation by 4.1-fold. There were significant increases in the phosphocontent of downstream PDGFR targets Akt and ERK1/2 (5.3-fold and 2.4-fold, respectively) that were inhibited by PDGF immunoneutralization or by the selective PDGFR inhibitor imatinib. Serum-free J774A.1-MacCM or RAW264.7-MacCM completely prevented 3T3-L1 preadipocyte apoptosis normally induced by serum deprivation. Addition of PDGF alone to serum-free control medium was sufficient to prevent 3T3-L1 preadipocyte apoptosis. Inhibition of PDGFR activation by MacCM, either by addition of imatinib or by PDGF immunodepletion of MacCM, effectively disrupted the prosurvival effect. In summary, our data indicate that MacCM promotes preadipocyte survival in a PDGFdependent manner.platelet-derived growth factor; obesity; macrophage OBESITY, defined as an increase in adiposity, results from a chronic positive energy balance. Expansion of adipose tissue occurs through the formation of new adipocytes, via the differentiation of stromal precursor preadipocytes, and the enlargement of existing adipocytes (9). Deficiency in the number of preadipocytes, or their capacity to differentiate, may lead to excessively hypertrophied and dysfunctional adipocytes that overproduce immune cell chemoattractant proteins (7,13,14). Concomitantly, the population of adipose tissue macrophages rises due to monocyte infiltration. This abnormal cellular remodeling of adipose tissue is associated with low-grade inflammation and insulin resistance (38,39).Paracrine communication among macrophages, adipocytes, and preadipocytes is believed to contribute to obesity-associated adipose tissue dysfunction (12). We and others have reported that macrophages produce anti-adipogenic factors that restrain the differentiation of preadipocytes into adipocytes (4,5,15,17,33,40). Macrophage-secreted factors have also been observed to have variable effects on preadipocyte proliferation (17,23). Apoptosis, the other key preadipocyte fate pertinent to adipose tissue remodeling (11, 21, 28), has not been evaluated with respect to potential macrophage paracrine interactions.The precise identity of the macrophage products influencing preadipocyte responses is not known. Here, we demonstrate th...

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Section: Discussionmentioning

confidence: 99%

Preadipocyte apoptosis is prevented by macrophage-conditioned medium in a PDGF-dependent manner

Molgat

Gagnon²,

Sorisky³

2009

American Journal of Physiology-Cell Physiology

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“…PDGFR-␤ is also expressed in the lens, and PDGF-D was recently found to be expressed in the iris and ciliary body leading to accumulation of PDGF-D protein in aqueous humor. In eye anterior segment organ culture, anti-PDGF-D specifically and potently inhibited lens epithelial cells proliferation, suggesting that PDGF-D secreted from the iris/ciliary body regulates lens epithelial proliferation (Ray et al 2005).…”

Section: Lensmentioning

confidence: 97%

Role of platelet-derived growth factors in physiology and medicine

Andræ¹,

Gallini²,

Betsholtz³

2008

Genes Dev.

2,075

1,898

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Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) have served as prototypes for growth factor and receptor tyrosine kinase function for more than 25 years. Studies of PDGFs and PDGFRs in animal development have revealed roles for PDGFR-␣ signaling in gastrulation and in the development of the cranial and cardiac neural crest, gonads, lung, intestine, skin, CNS, and skeleton. Similarly, roles for PDGFR-␤ signaling have been established in blood vessel formation and early hematopoiesis. PDGF signaling is implicated in a range of diseases. Autocrine activation of PDGF signaling pathways is involved in certain gliomas, sarcomas, and leukemias. Paracrine PDGF signaling is commonly observed in epithelial cancers, where it triggers stromal recruitment and may be involved in epithelial-mesenchymal transition, thereby affecting tumor growth, angiogenesis, invasion, and metastasis. PDGFs drive pathological mesenchymal responses in vascular disorders such as atherosclerosis, restenosis, pulmonary hypertension, and retinal diseases, as well as in fibrotic diseases, including pulmonary fibrosis, liver cirrhosis, scleroderma, glomerulosclerosis, and cardiac fibrosis. We review basic aspects of the PDGF ligands and receptors, their developmental and pathological functions, principles of their pharmacological inhibition, and results using PDGF pathway-inhibitory or stimulatory drugs in preclinical and clinical contexts.Platelet-derived growth factor (PDGF) was identified more than three decades ago as a serum growth factor for fibroblasts, smooth muscle cells (SMCs), and glia cells (Kohler and Lipton 1974;Ross et al. 1974;Westermark and Wasteson 1976). Human PDGF was originally identified as a disulfide-linked dimer of two different polypeptide chains, A and B, separable using reversed phase chromatography (Johnsson et al. 1982). The B-chain (PDGF-B) was characterized by amino acid sequencing, revealing a close homology between PDGF-B and the product of the retroviral oncogene v-sis of simian sarcoma virus (SSV) (Doolittle et al. 1983;Waterfield et al. 1983). Subsequent studies confirmed that the human cellular counterpart (c-sis) was identical to PDGF-B and that autocrine PDGF activity was sufficient for SSV transformation in vitro. This was a paradigm-shifting discovery about the relationship between neoplastic cell transformation and normal growth control. For the first time, the importance of autocrine growth stimulation in neoplastic transformation was demonstrated. As discussed below, it is now well established that autocrine PDGF stimulation plays a role also in some human cancers.PDGF-A was characterized by cDNA cloning ). This resolved a paradoxical lack of correlation between secretion of PDGF-like growth factors from tumor cell lines and their expression of c-sis; it turned out that most such cell lines express PDGF-A and secrete PDGF-AA homodimers ). Together with the demonstration that PDGF-BB homodimers are produced by SSV-transformed or PDGF-Bexpressing cells, these results showed that the PDGF...

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“…Hence, growth factors in the environment are thought to be responsible for maintaining epithelium and fibers. Growth factors including FGF-1 and FGF-2 [96], PDGF [97], PDGF-D [98], insulin/IGF1 [99][100][101], EGF/TGFα [101,102], and HGF [103,104] all have been shown to stimulate lens epithelial cell proliferation in the cultured epithelial cells of a variety of species including chick, rat and human, epithelial explant cultures, or whole lens cultures (for review see [105]). On the other hand, TGFβ has been shown to inhibit the proliferation of human lens epithelial cells in culture [106].…”

Section: Growth Factors and Their Receptors Affecting Lens Cell Prolimentioning

confidence: 99%

“…For example, PDGF-A and its receptor PDGFR-α are expressed in the proliferating cells of the epithelium [108]. PDGF-D is expressed in iris and ciliary body and this growth factor is found in aqueous humor [98]. FGFs -1 and -2 are expressed in the lens as well as in surrounding ocular tissues [109].…”

Section: Growth Factors and Their Receptors Affecting Lens Cell Prolimentioning

confidence: 99%

Cell cycle regulation in the developing lens

Griep¹

2006

Seminars in Cell & Developmental Biology

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Regulation of cell proliferation is a critical aspect of the development of multicellular organisms. The ocular lens is an excellent model system in which to unravel the mechanisms controlling cell proliferation during development. In recent years, several cell cycle regulators have been shown to be essential for maintaining normal patterns of lens cell proliferation. Additionally, many growth factor signaling pathways and cell adhesion factors have been shown to have the capacity to regulate lens cell proliferation. Given this complexity, understanding the cross talk between these many signaling pathways and how they are coordinated are important directions for the future.

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Platelet-derived Growth Factor D, Tissue-specific Expression in the Eye, and a Key Role in Control of Lens Epithelial Cell Proliferation

Abstract: Platelet-derived growth factor D (PDGF-D

Cited by 30 publications

References 34 publications

Preadipocyte apoptosis is prevented by macrophage-conditioned medium in a PDGF-dependent manner

Preadipocyte apoptosis is prevented by macrophage-conditioned medium in a PDGF-dependent manner

Role of platelet-derived growth factors in physiology and medicine

Cell cycle regulation in the developing lens

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