scholarly journals Heparin-binding EGF-like growth factor mRNA is upregulated in the peri-infarct region of the remnant kidney model: in vitro evidence suggests a regulatory role in myofibroblast transformation.

1998 ◽  
Vol 9 (8) ◽  
pp. 1464-1473
Author(s):  
G Kirkland ◽  
K Paizis ◽  
L L Wu ◽  
M Katerelos ◽  
D A Power
Keyword(s):  
Endothelial Cells ◽  
In Situ Hybridization ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Human Fibroblasts ◽  
Renal Infarction ◽  
Heparin Binding ◽  
Alpha Smooth Muscle Actin

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a potent fibroblast and epithelial cell mitogen that may be important in wound healing. The aim of this study was to determine its distribution and possible function in segmental renal infarction. At day 1 postinfarction, in situ hybridization showed that HB-EGF mRNA was markedly increased by tubular epithelial cells bordering the infarcted zone. At day 3, typical myofibroblasts expressing alpha-smooth muscle actin (alpha-SMA) were present in large numbers at the peri-ischemic border and, over succeeding days, were also seen within the infarcted area. Some of these cells expressed HB-EGF mRNA by in situ hybridization suggesting possible autocrine stimulation. Endothelial cells appeared to be more resistant to ischemia than tubules because some capillaries at the periphery of the infarct, surrounded by infarcted tubules, also expressed HB-EGF mRNA. The staining intensity of HB-EGF mRNA in individual tubules and endothelial cells was maximal at day 5 after infarction, although Northern blots of tissue from the peri-infarct area only showed significantly increased expression of HB-EGF mRNA at days 1 and 3, perhaps reflecting a smaller area of greater intensity of expression at day 5. Because tubular cells expressing high levels of HB-EGF mRNA were directly apposed to myofibroblasts, an attempt was made to determine whether HB-EGF contributed to upregulation of alpha-SMA by human fibroblasts. Although stimulation of the fibroblast cell line MRC-5 with transforming growth factor-beta1 (TGF-beta1) increased alpha-SMA, HB-EGF reduced expression. HB-EGF also strongly inhibited the increased expression of alpha-SMA due to TGF-beta1. Because HB-EGF is a potent fibroblast mitogen and TGF-beta is usually antiproliferative, this study suggests that HB-EGF may contribute to a local balance between fibroblast proliferation and differentiation into myofibroblasts during scarring.

scholarly journals Regulation of Cellular Senescence Is Independent from Profibrotic Fibroblast-Deposited ECM

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1628
Author(s):  
Kaj E. C. Blokland ◽  
Habibie Habibie ◽  
Theo Borghuis ◽  
Greta J. Teitsma ◽  
Michael Schuliga ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cellular Senescence ◽  
Transforming Growth Factor ◽  
Cell Function ◽  
Smooth Muscle Actin ◽  
Transforming Growth Factor Β1 ◽  
Tissue Growth ◽  
Alveolar Epithelial Cells ◽  
Lung Fibroblasts ◽  
Alpha Smooth Muscle Actin

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with poor survival. Age is a major risk factor, and both alveolar epithelial cells and lung fibroblasts in this disease exhibit features of cellular senescence, a hallmark of ageing. Accumulation of fibrotic extracellular matrix (ECM) is a core feature of IPF and is likely to affect cell function. We hypothesize that aberrant ECM deposition augments fibroblast senescence, creating a perpetuating cycle favouring disease progression. In this study, primary lung fibroblasts were cultured on control and IPF-derived ECM from fibroblasts pretreated with or without profibrotic and prosenescent stimuli, and markers of senescence, fibrosis-associated gene expression and secretion of cytokines were measured. Untreated ECM derived from control or IPF fibroblasts had no effect on the main marker of senescence p16Ink4a and p21Waf1/Cip1. However, the expression of alpha smooth muscle actin (ACTA2) and proteoglycan decorin (DCN) increased in response to IPF-derived ECM. Production of the proinflammatory cytokines C-X-C Motif Chemokine Ligand 8 (CXCL8) by lung fibroblasts was upregulated in response to senescent and profibrotic-derived ECM. Finally, the profibrotic cytokines transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) were upregulated in response to both senescent- and profibrotic-derived ECM. In summary, ECM deposited by IPF fibroblasts does not induce cellular senescence, while there is upregulation of proinflammatory and profibrotic cytokines and differentiation into a myofibroblast phenotype in response to senescent- and profibrotic-derived ECM, which may contribute to progression of fibrosis in IPF.

Expression of transforming growth factor alpha during development

1988 ◽  
Vol 66 (8) ◽  
pp. 1113-1121 ◽  
Author(s):  
V. K. M. Han ◽  
A. J. D'Ercole ◽  
D. C. Lee
Keyword(s):  
In Situ Hybridization ◽  
Growth Factor ◽  
Mrna Expression ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Alpha ◽  
Egf Receptors ◽  
Hybridization Histochemistry ◽  
In Situ Hybridization Histochemistry ◽  
Factor Alpha

Transforming growth factors (TGFs) are polypeptides that are produced by transformed and tumour cells, and that can confer phenotypic properties associated with transformation on normal cells in culture. One of these growth-regulating molecules, transforming growth factor alpha (TGF-α), is a 50 amino acid polypeptide that is related to epidermal growth factor (EGF) and binds to the EGF receptor. Previous studies have shown that TGF-α is expressed during rodent embryogenesis between 7 and 14 days gestation. To investigate the cellular sites of TGF-α mRNA expression during development, we have performed Northern analyses and in situ hybridization histochemistry on the conceptus and maternal tissues at various gestational ages. Contrary to previous reports, both Northern analyses and in situ hybridization histochemistry indicate that TGF-α mRNA is predominantly expressed in the maternal decidua and not in the embryo. Decidual expression is induced following implantation, peaks at day 8, and declines through day 15 when the decidua is being resorbed. In situ hybridization revealed that expression of TGF-α mRNA is highest in the region of decidua adjacent to the embryo and is low or nondetectable in the uterus, placenta, and embryo. In addition, we could not detect TGF-α mRNA expression in other maternal tissues, indicating that the induction of TGF-α transcripts in the decidua is tissue specific, and not a pleiotropic response to changes in hormonal milieu that occur during pregnancy. The developmentally regulated expression of TGF-α mRNA in the decidua, together with the presence of EGF receptors in this tissue, suggests that this peptide may stimulate mitosis and angiogenesis locally by an autocrine mechanism. Because EGF receptors are also present in the embryo and placenta, TGF-α may act on these tissues by a paracrine or endocrine mechanism.

scholarly journals Synthesis of transforming growth factor-beta 1 by megakaryocytes and its localization to megakaryocyte and platelet alpha-granules

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 1946-1955 ◽  
Author(s):  
RA Fava ◽  
TT Casey ◽  
J Wilcox ◽  
RW Pelton ◽  
HL Moses ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Messenger Rna ◽  
Transforming Growth Factor ◽  
Immunoperoxidase Technique ◽  
Storage Site ◽  
Tgf Beta ◽  
Growth Factor Beta

We have directly demonstrated that megakaryocytes are a major site of synthesis and storage of transforming growth factor-beta 1 (TGF/beta 1) by combined immunohistochemical, immunocytochemical, and in situ hybridization methods. The presence of TGF/beta 1 messenger RNA (mRNA) in mature megakaryocytes in adult rat spleen and bone marrow (BM) was established by in situ hybridization. Localization of TGF/beta 1 protein to intact alpha-granules of megakaryocytes, its putative storage site, was accomplished in glycol-methacrylate embedded porcine BM with an immunoperoxidase technique and light microscopy. The TGF/beta 1 was sequestered in intracytoplasmic granules in a pattern virtually identical to that of another alpha-granule marker protein, fibrinogen. This observation strongly suggests packaging of TGF/beta 1 into this organelle within megakaryocytes. That TGF/beta 1 mRNA was localized to megakaryocytes suggests that the TGF/beta 1 found in the alpha-granules in platelets originates with megakaryocyte synthesis. The alpha-granule localization of TGF/beta 1, as well as fibrinogen, was also demonstrated in isolated platelets at the ultrastructural level by electronmicroscopy (EM) and postembedding colloidal-gold immunocytochemistry, thus directly demonstrating that alpha-granules are the final storage site for TGF/beta 1 in mature platelets.

scholarly journals Reduced pericyte and tight junction coverage in old diabetic rats are associated with hyperglycemia-induced cerebrovascular pericyte dysfunction

2020 ◽  
Author(s):  
Yedan Liu ◽  
Huawei Zhang ◽  
Shaoxun Wang ◽  
Ya Guo ◽  
Xing Fang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Tight Junction ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Cognitive Impairments ◽  
Cerebral Hemodynamics ◽  
Alpha Smooth Muscle Actin ◽  
Atp Production

Diabetes mellitus (DM) is one of the primary pathological factors that contributes to aging-related cognitive impairments, but the underlying mechanisms remain unclear. We recently reported that old DM rats exhibited impaired myogenic responses of the cerebral arteries and arterioles, poor cerebral blood flow autoregulation, enhanced blood-brain barrier (BBB) leakage, and cognitive impairments. These changes were associated with diminished vascular smooth muscle cell contractile capability linked to elevated reactive oxygen species (ROS) and reduced ATP production. The present study, using a non-obese T2DN DM rat, isolated parenchymal arterioles (PAs), and cultured cerebral microvascular pericytes, examined whether cerebrovascular pericyte in DM is damaged and whether pericyte dysfunction may play a role in the regulation of cerebral hemodynamics and BBB integrity. We found that ROS and mitochondrial superoxide production were elevated in PAs isolated from old DM rats and in high glucose (HG)-treated alpha-smooth muscle actin positive pericytes. HG-treated pericytes displayed decreased contractile capability in association with diminished mitochondrial respiration and ATP production. Additionally, the expression of advanced glycation end products, transforming growth factor-beta, vascular endothelial growth factor, and fibronectin were enhanced, but claudin 5 and integrin β1 was reduced in the brain of old DM rats and HG-treated pericytes. Further, endothelial tight junction and pericyte coverage on microvessels were reduced in the cortex of old DM rats. These results demonstrate our previous findings that the impaired cerebral hemodynamics and BBB leakage and cognitive impairments in the same old DM model are associated with hyperglycemia-induced cerebrovascular pericyte dysfunction.

Transforming growth factor-α and oral fibroma: immunohistochemical and in situ hybridization study

2003 ◽  
Vol 61 (12) ◽  
pp. 1449-1454 ◽  
Author(s):  
Horatiu Rotaru ◽  
Je-Yong Choi ◽  
Sam-Pyo Hong ◽  
Yong-Chan Lee ◽  
Kyoung-In Yun ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Hybridization Study ◽  
Transforming Growth Factor Α ◽  
Factor Α

Vascular Endothelial Growth Factor Expression in Peritoneal Mesothelial Cells Undergoing Transdifferentiation

2008 ◽  
Vol 28 (5) ◽  
pp. 497-504 ◽  
Author(s):  
Jing Zhang ◽  
Kook-Hwan Oh ◽  
Hui Xu ◽  
Peter J. Margetts
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Vascular Endothelial ◽  
Alpha Smooth Muscle Actin ◽  
Peritoneal Tissue ◽  
Peritoneal Mesothelium ◽  
Endothelial Growth Factor

Objective To analyze gene expression of localized peritoneal tissue structures in a rodent model of peritoneal fibrosis. Methods Female Sprague Dawley rats were treated with an intraperitoneal injection of an adenovirus expressing active transforming growth factor-beta or control adenovirus. Four and 7 days after infection, animals were sacrificed and frozen sections of parietal peritoneum were subjected to immunofluorescence-aided laser capture microdissection in order to isolate vascular, mesothelial, and submesothelial structures. RNA was extracted from microdissected tissue and gene expression was analyzed by quantitative reverse-transcript polymerase chain reaction. We analyzed genes involved in angiogenesis, epithelial-to-mesenchymal transdifferentiation, and fibrosis. Vascular endothelial growth factor and alpha-smooth muscle actin expression was analyzed with immunohistochemistry of formalin-fixed tissue. Results Transforming growth factor-β1 induced expression of Snail and alpha-smooth muscle actin genes in the peritoneal mesothelium. This same cell population also demonstrated increased gene expression of vascular endothelial growth factor. The distribution of this growth factor was confirmed by immunohistochemistry. The fibrogenic growth factor, connective tissue growth factor, was also strongly induced in the peritoneal mesothelium. Conclusions Using immunofluorescence-aided laser capture microdissection, we were able to study gene expression in subcompartments of the peritoneal tissue. We demonstrated that mesothelial cells exhibiting mesenchymal transdifferentiation are associated with increased expression of genes associated with fibrosis and angiogenesis.

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