Transgenic
            <i>LacZ</i>
            under control of
            <i>Hec-6st</i>
            regulatory sequences recapitulates endogenous gene expression on high endothelial venules

Liao, Shan; Bentley, Kevin L.; Lebrun, Marielle; Lesslauer, Werner; Ruddle, Frank H.; Ruddle, Nancy H.

doi:10.1073/pnas.0700334104

Cited by 21 publications

(28 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…LVs that are packed with lymphocytes are prominent in some TLOs (ref. 36 and Figure 2), which suggests that they do transport lymphocytes. Additional evidence supporting an afferent function for TLO LVs comes from the study of myasthenia gravis (MG), an autoimmune disease characterized by thymic TLOs with HEVs and B cell follicles.…”

Section: Functions Of Lvs In Tlosmentioning

confidence: 86%

Lymphatic vessels and tertiary lymphoid organs

Ruddle¹

2014

J. Clin. Invest.

Self Cite

158

124

View full text Add to dashboard Cite

Section: Functions Of Lvs In Tlosmentioning

confidence: 86%

Lymphatic vessels and tertiary lymphoid organs

Ruddle¹

2014

J. Clin. Invest.

Self Cite

158

124

View full text Add to dashboard Cite

“…First-strand cDNA was synthesized from DNase-treated RNA from each sample using oligo (dT) [12][13][14][15][16][17][18] and Superscript II reverse transcriptase (RT; Invitrogen). cDNA was used for PCR amplifications using gene-specific primer sets and conditions.…”

Section: Rt-pcrmentioning

confidence: 99%

“…13 Lymphangiogenesis has been described in TLOs in thyroiditis, sialitis, rheumatoid arthritis, and chronic kidney graft rejection. [14][15][16][17] LTs, key mediators of inflammation through the induction of chemokines and vascular adhesion molecules, 18 also play crucial roles in lymphoid organ development. 19 The homotrimer LT␣ 3 is secreted by CD4 ϩ Th1, CD8 ϩ , NK, B, and lymphoid tissue inducer cells and signals through TNFR1 and TNFR2, explaining its partial redundancy to TNF␣ 3 , which signals through the same receptors.…”

Section: Introductionmentioning

confidence: 99%

Lymphotoxin-alpha contributes to lymphangiogenesis

Mounzer

Svendsen

Bałuk

et al. 2010

Blood

Self Cite

View full text Add to dashboard Cite

Lymphotoxin-␣ (LT␣), IntroductionRecent years have seen great advances in the molecular understanding of lymphatic vessels and lymphangiogenesis. 1 Studies with genetically engineered mice identified several key growth factors, transcription factors, transmembrane glycoproteins, and signaling proteins that are crucial for lymphatic vessel development and function. [2][3][4][5] Varying deficiencies in these critical molecules resulted in a spectrum of lymphedema phenotypes ranging from edematous embryos with chylous ascites and severe vascular defects associated with perinatal lethality, 3,6 to more subtle manifestations of lymphatic function defects. [7][8][9] Derangements in the structure or function of lymphatic vessels may induce edema. 1 Chy mice, in which a heterozygous mutation in the Vegfr3 gene results in inactivation of vascular endothelial growth factor 3 (VEGFR-3) signaling, exhibit lymphedema only in the fore and hind paws despite an absence of lymphatics in the entire dermis, thus demonstrating the effectiveness of compensatory mechanisms. 9 Lymphangiogenesis has been shown to occur at the sites of inflammation in models of corneal transplantation and airway infection. [10][11][12] During chronic inflammation in autoimmunity, graft rejection and infection, chronic accumulations of lymphoid cells that resemble lymph nodes, termed "tertiary lymphoid organs" (TLOs) develop, many of which require members of the lymphotoxin (LT)/TNF family. 13 Lymphangiogenesis has been described in TLOs in thyroiditis, sialitis, rheumatoid arthritis, and chronic kidney graft rejection. [14][15][16][17] LTs, key mediators of inflammation through the induction of chemokines and vascular adhesion molecules, 18 also play crucial roles in lymphoid organ development. 19 The homotrimer LT␣ 3 is secreted by CD4 ϩ Th1, CD8 ϩ , NK, B, and lymphoid tissue inducer cells and signals through TNFR1 and TNFR2, explaining its partial redundancy to TNF␣ 3 , which signals through the same receptors. 20 TNF␣ is made by a wider variety of cells, including macrophages, in addition to the LT␣-producing lymphocytes. The LT␣ monomer also forms a heterotrimer with LT␤ that is required for the cell surface expression of the LT␣␤ complex. 21 The LT␣ 1 ␤ 2 complex binds to and signals through the LT␤R. Mice deficient in LT␣ lack all lymph nodes and Peyer patches, 19 whereas those deficient in LT␤ retain some cervical, sacral, and mesenteric lymph nodes. 22 Transgenic expression of mouse LT␣ under the control of the rat insulin promoter II (RIP) leads to its expression in the ␤ cells of the islets of Langerhans in the pancreas as expected, and in the skin 23 and proximal convoluted tubules of the kidney 23,24 as this promoter is somewhat "leaky." These mice develop accumulations of T and B cells, dendritic cells, follicular dendritic cells, and macrophages that are organized into TLOs that resemble lymph nodes in cellular composition and compartmentalization, the presence of high endothelial venules (HEVs) and lymphoid chemokine expression, 18,25 du...

show abstract

“…An AT2R gene fragment was cloned into the expression vector containing TetO repeat sequence, i.e., pUHD10-3, by homologous recombination (14) to establish Doxycycline-regulated mammalian expression system (DoxOn system) containing regulatory plasmid pUHD 17-1hyg, mammalian expression plasmid pUHD 10-3/AT2R, fluorescence reporter plasmid pUHC 13-3 and neomycin screening-resistant simple plasmid pSV2 neo (15,16). pUHD 17-1hyg, 6,484 bp in length, was derived from pBR322 and contained human cytomegalovirus (hCMV) promoter and chimeric tetracycline induced transactivator (rtTA) encoding sequence.…”

Section: Methodsmentioning

confidence: 99%

Conditional expression of type 2 angiotensin II receptor in rat vascular smooth muscle cells reveals the interplay of the angiotensin system in matrix metalloproteinase 2 expression and vascular remodeling

Tao

Wang²,

Srivenugopal³

et al. 2009

Int J Mol Med

View full text Add to dashboard Cite

Abstract. Angiotensin II is well implicated in neointimal proliferation and the resulting restenosis, however, the mechanisms involved remain unclear. The type 2 angiotensin II (AT2) receptor, largely unexpressed in the adult vasculature, however, appears at significant levels after vascular injury. To investigate the specific contribution of AT2 receptor and the interplay of the angiotensin system to neointima, we engineered rat vascular smooth muscle cells (VSMCs) to express the AT2 receptor in a tetracycline-regulated system. Several VSMC clones resistant to both hygromycin and G418 were selected, many of which showed high, but regulatable levels of AT2R expression within 48 h of doxycycline (Dox) exposure. In untransfected VSMCs and stable transfectants with no AT2R induction, Ang II significantly increased the expression of matrix metalloproteinase 2 (MMP-2), which is linked to neointimal growth. However, induction of AT2R by Dox addition markedly decreased MMP-2 levels (P<0.01) and this downregulation was further promoted by CV-11974, a specific antagonist of AT1 receptor. In contrast, the PD123319 compound, which selectively curtails the AT2 receptor, reversed the inhibition caused by CV-11974. We conclude that Ang II enhances the MMP-2 expression via AT1R, and that enforces AT2R inhibited the same. These data confirm that AT2R functions to downregulate the effects elicited by Ang II + AT1R signaling and point to the role of MMP and extracellular matrix in vascular injury. The findings provide fresh experimental approaches to prevent or control restenosis through transduction of VSMCs expressing optimal levels of AT2R.

show abstract

Transgenic LacZ under control of Hec-6st regulatory sequences recapitulates endogenous gene expression on high endothelial venules

Cited by 21 publications

References 43 publications

Lymphatic vessels and tertiary lymphoid organs

Lymphatic vessels and tertiary lymphoid organs

Lymphotoxin-alpha contributes to lymphangiogenesis

Conditional expression of type 2 angiotensin II receptor in rat vascular smooth muscle cells reveals the interplay of the angiotensin system in matrix metalloproteinase 2 expression and vascular remodeling

Contact Info

Product

Resources

About