Inhibins and activins regulate mammary epithelial cell differentiation through mesenchymal-epithelial interactions

Development ◽  
1997 ◽  
Vol 124 (14) ◽  
pp. 2701-2708 ◽  
Author(s):  
G.W. Robinson ◽  
L. Hennighausen
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cell ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Mammary Epithelial ◽  
Wild Type ◽  
Epithelial Cell Differentiation ◽  
Ductal Elongation ◽  
Transplantation Experiments

Inhibins and activins are members of the transforming growth factor beta (TGFbeta) family. Female mice in which both alleles encoding the inhibin betaB subunit have been deleted are unable to nurse their pups. We have now identified a cause of lactation failure in these mice. Ductal elongation and alveolar morphogenesis are retarded. During puberty and pregnancy, ductal outgrowth and alveolar development are limited and morphologically abnormal endbuds persist in the glands of postpartum females. The alveolar lumina fail to expand at parturition due to the absence of secreted milk. Transplantation experiments have been performed to determine whether the absence of systemic- or mammary-derived betaB subunits are the cause for the incomplete and aberrant development. While transplanted intact glands from wild-type mice grew normally in betaB-deficient hosts, betaB-deficient glands remained underdeveloped in wild-type hosts. However, betaB-deficient epithelium developed normally when transplanted into the fat pad of wild-type hosts. This demonstrates that ductal elongation and epithelial cell differentiation during puberty and pregnancy require activin/inhibin signalling from the stroma. The results further show that distinct, though related, activins and inhibins perform unique functions and are not able to compensate for the absence of activin B and AB and inhibin B in the process of mammogenesis. The betaB-deficient mice provide the first genetic evidence for stromal signalling in the adult mammary gland in vivo.

Late gestational hyperprolactinemia accelerates mammary epithelial cell differentiation that leads to increased milk yield1

2013 ◽  
Vol 91 (3) ◽  
pp. 1102-1111 ◽  
Author(s):  
M. K. VanKlompenberg ◽  
R. Manjarin ◽  
J. F. Trott ◽  
H. F. McMicking ◽  
R. C. Hovey
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cell ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial ◽  
Epithelial Cell Differentiation

scholarly journals Image-based evaluation of the molecular events underlying HC11 mammary epithelial cell differentiation

2008 ◽  
Vol 382 (2) ◽  
pp. 122-128 ◽  
Author(s):  
Liang Shan ◽  
Renshu Zhang ◽  
Wanghai Zhang ◽  
Edward Lee ◽  
Rajagopalan Sridhar ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cell ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial ◽  
Epithelial Cell Differentiation ◽  
Molecular Events

Localized distribution of alpha 9 integrin in the cornea and changes in expression during corneal epithelial cell differentiation.

1995 ◽  
Vol 43 (4) ◽  
pp. 353-362 ◽  
Author(s):  
M A Stepp ◽  
L Zhu ◽  
D Sheppard ◽  
R L Cranfill
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cell ◽  
Corneal Epithelium ◽  
Corneal Epithelial Cell ◽  
Basal Cells ◽  
Postnatal Maturation ◽  
Central Cornea ◽  
Epithelial Cell Differentiation

A recently characterized integrin alpha-chain, alpha 9, forms heterodimers with the integrin beta 1-chain and is present in the skin with a distribution similar to that of alpha 2 and alpha 3, other beta 1 integrins. To determine whether alpha 9 is expressed in the stratified squamous epithelium of the cornea, we used immunohistochemical techniques to compare the distribution of alpha 9 in the adult mouse cornea with that of alpha 3. Abundant alpha 9 was expressed in the lateral and basal membranes of the basal cells of the conjunctiva and corneal limbus, but very little alpha 9 was present in the basal cells of the central corneal epithelium. In contrast, alpha 3 was present in the membranes of basal cells of the conjunctiva, limbus, and central cornea. To determine when during postnatal maturation of the corneal epithelium alpha 9 becomes restricted to the limbus, we looked at the distribution of alpha 9 and alpha 3 in the developing mouse eye from birth to eyelid opening. At birth, the basal cells of the cornea and developing limbal region did not express alpha 9, but there was abundant alpha 9 expressed in suprabasal cells between the fused lids and in the basal cells of the skin and conjunctiva. In contrast, alpha 3, integrin was expressed uniformly in the basal cells across the surface of the conjunctiva, limbus, and cornea and was present only in the basal cells of the epithelium between the fused eyelids. In the central cornea, alpha 9 expression increased in basal cells up until Day 10 after birth. After Day 10, alpha 9 expression in the central cornea began to decrease; after the lids were open, alpha 9 expression in the central cornea became restricted to the limbus. In the basal and suprabasal cells between the fused eyelids expression of alpha 9 became increasingly restricted over time to the basal cells. Recent data suggest that alpha 9 beta 1 can interact with tenascin. Our dual labeling confocal microscopy studies indicate that localization of alpha 9 and tenascin are not coordinated in the developing mouse cornea. Many recent studies have shown an important role for beta 1 integrins in mediating epithelial cell differentiation in vitro; in vivo, changes in integrin expression have been found in wound healing, psoriasis, and in basal and squamous cell carcinomas.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Deletion of SOCS2 Reduces Post-Colitis Fibrosis via Alteration of the TGFβ Pathway

2020 ◽  
Vol 21 (9) ◽  
pp. 3073
Author(s):  
Amna Al-Araimi ◽  
Amira Al Kharusi ◽  
Asma Bani Oraba ◽  
Matar M Al-Maney ◽  
Shadia Al Sinawi ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Recovery Period ◽  
Cytokine Signaling ◽  
Protective Effects ◽  
Wild Type ◽  
Epithelial Proliferation

Inflammatory bowel disease (IBD) is an immunologically mediated chronic intestinal disorder. Growth hormone (GH) administration enhances mucosal repair and decreases intestinal fibrosis in patients with IBD. In the present study, we investigated the effect of cellular sensitivity to GH via suppressor of cytokine signaling 2 (SOCS2) deletion on colitis and recovery. To induce colitis, wild type and SOCS2 knockout (SOCS2−/−) mice were treated with 3% dextran sodium sulphate (DSS), followed by a recovery period. SOCS2−/− mice showed higher disease activity during colitis with increased mRNA expression of the pro-inflammatory cytokines nitric oxide synthase 2 (NOS2) and interleukin 1 β (IL1-β). At recovery time point, SOCS2−/− showed better recovery with less fibrosis measured by levels of α-SMA and collagen deposition. Protein and mRNA expressions of transforming growth factor beta β1 (TGF-β1) receptors were significantly lower in SOCS2−/− mice compared to wild-type littermates. Using an in vivo bromodeoxyuridine (BrdU) proliferation assay, SOCS2−/− mice showed higher intestinal epithelial proliferation compared to wild-type mice. Our results demonstrated that deletion of the SOCS2 protein results in higher growth hormone sensitivity associated with higher pro-inflammatory signaling; however, it resulted in less tissue damage with less fibrotic lesions and higher epithelial proliferation, which are markers of GH-protective effects in IBD. This suggests a pleiotropic effect of SOCS2 and multiple cellular targets. Further study is required to study role of SOCS2 in regulation of TGFβ-mothers against the decapentaplegic homolog (Smad) pathway.

scholarly journals Cell cycle-targeting microRNAs promote differentiation by enforcing cell-cycle exit

2017 ◽  
Vol 114 (40) ◽  
pp. 10660-10665 ◽  
Author(s):  
Tobias Otto ◽  
Sheyla V. Candido ◽  
Mary S. Pilarz ◽  
Ewa Sicinska ◽  
Roderick T. Bronson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Differentiation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Airway Disease ◽  
Quiescent State ◽  
Cell Cycle Exit ◽  
Epithelial Cell Differentiation ◽  
Chronic Airway Disease

MicroRNAs (miRNAs) have been known to affect various biological processes by repressing expression of specific genes. Here we describe an essential function of the miR-34/449 family during differentiation of epithelial cells. We found that miR-34/449 suppresses the cell-cycle machinery in vivo and promotes cell-cycle exit, thereby allowing epithelial cell differentiation. Constitutive ablation of all six members of this miRNA family causes derepression of multiple cell cycle-promoting proteins, thereby preventing epithelial cells from exiting the cell cycle and entering a quiescent state. As a result, formation of motile multicilia is strongly inhibited in several tissues such as the respiratory epithelium and the fallopian tube. Consequently, mice lacking miR-34/449 display infertility as well as severe chronic airway disease leading to postnatal death. These results demonstrate that miRNA-mediated repression of the cell cycle is required to allow epithelial cell differentiation.

scholarly journals Disruption of transforming growth factor beta signaling by a mutation that prevents transphosphorylation within the receptor complex.

1995 ◽  
Vol 15 (3) ◽  
pp. 1573-1581 ◽  
Author(s):  
J Cárcamo ◽  
A Zentella ◽  
J Massagué
Keyword(s):  
Growth Factor ◽  
Ligand Binding ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Signal Propagation ◽  
Tgf Beta ◽  
Wild Type ◽  
Growth Factor Beta ◽  
Signaling Activity

T beta R-II (transforming growth factor beta [TGF-beta] type II receptor) is a transmembrane serine/threonine kinase that acts as the primary TGF-beta receptor. Ligand binding to T beta R-II leads to the recruitment and phosphorylation of T beta R-I, a distantly related transmembrane kinase that acts as a downstream signaling component. T beta R-I phosphorylation by T beta R-II is shown here to be essential for signaling. A mutant T beta R-II that binds ligand but lacks signaling activity was identified. This mutant was identified by screening with a TGF-beta-inducible vector a series of mink lung epithelial cell clones that have normal TGF-beta binding activity but have lost antiproliferative and transcriptional responses to TGF-beta. When transiently cotransfected with T beta R-II, one of these cell lines, S-21, recovered TGF-beta responsiveness. cDNA cloning and sequencing of T beta R-II from S-21 cells revealed a point mutation that changes proline 525 to leucine in kinase subdomain XI. A recombinant receptor containing this mutation, T beta R-II(P525L), is similar to wild-type T beta R-II in its abilities to bind ligand, support ligand binding to T beta R-I, and form a complex with T beta R-I in vivo. T beta R-II(P525L) has autophosphorylating activity in vitro and in vivo; however, unlike the wild-type receptor, it fails to phosphorylate an associated T beta R-I. These results suggest that T beta R-II(P525L) is a catalytically active receptor that cannot recognize T beta R-I as a substrate. The close link between T beta R-I transphosphorylation and signaling activity argues that transphosphorylation is essential for signal propagation via T beta R-I.

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