Searching the Resource Information Network

Our searching services are busy right now. Please try again later

  • Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Intrabody against prolyl hydroxylase 2 promotes angiogenesis by stabilizing hypoxia-inducible factor-1α.

Liangzhong Zhao | Ziyu Liu | Fang Yang | Ying Zhang | Ying Xue | Haipeng Miao | Xiangzhi Liao | Hongli Huang | Guiying Li
Scientific reports | 2019

Hypoxia-inducible factor (HIF)-1α is a crucial transcription factor that regulates the expression of target genes involved in angiogenesis. Prolyl hydroxylase 2 (PHD2) dominantly hydroxylates two highly conserved proline residues of HIF-1α to promote its degradation. This study was designed to construct an intrabody against PHD2 that can inhibit PHD2 activity and promote angiogenesis. Single-chain variable fragment (scFv) against PHD2, INP, was isolated by phage display technique and was modified with an endoplasmic reticulum (ER) sequence to obtain ER-retained intrabody against PHD2 (ER-INP). ER-INP was efficiently expressed and bound to PHD2 in cells, significantly increased the levels of HIF-1α, and decreased hydroxylated HIF-1α in human embryonic kidney cell line (HEK293) cells and mouse mononuclear macrophage leukaemia cell line (RAW264.7) cells. ER-INP has shown distinct angiogenic activity both in vitro and in vivo, as ER-INP expression significantly promoted the migration and tube formation of human umbilical vein endothelial cells (HUVECs) and enhanced angiogenesis of chick chorioallantoic membranes (CAMs). Furthermore, ER-INP promoted distinct expression and secretion of a range of angiogenic factors. To the best of our knowledge, this is the first study to report an ER-INP intrabody enhancing angiogenesis by blocking PHD2 activity to increase HIF-1α abundance and activity. These results indicate that ER-INP may play a role in the clinical treatment of tissue injury and ischemic diseases in the future.

Pubmed ID: 31413262

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


SPSS (tool)

RRID:SCR_002865

Software package used for interactive, or batched, statistical analysis in social science, health sciences and marketing. Software platform offers advanced statistical analysis, a library of machine-learning algorithms, text analysis, open-source extensibility, integration with big data and deployment into applications.Versions that were produced by SPSS Inc. before the IBM acquisition (Versions 18 and earlier) would be given origin or publisher of SPSS Inc. in Chicago.

View all literature mentions

Novus Biologicals (tool)

RRID:SCR_004286

Commercial antibody vendor which supplies antibodies and other products to life science researchers.

View all literature mentions

Cell Signaling Technology (tool)

RRID:SCR_004431

Privately held company that develops and produces antibodies, ELISA kits, ChIP kits, proteomic kits, and other related reagents used to study cell signaling pathways that impact human health.

View all literature mentions

Millipore (tool)

RRID:SCR_008983

An Antibody supplier

View all literature mentions

Abcam (tool)

RRID:SCR_012931

A commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.

View all literature mentions

BD Biosciences (tool)

RRID:SCR_013311

An Antibody supplier

View all literature mentions

HEK293 (tool)

RRID:CVCL_0045

Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions

Hep-G2 (tool)

RRID:CVCL_0027

Cell line Hep-G2 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

RAW 264.7 (tool)

RRID:CVCL_0493

Cell line RAW 264.7 is a Cancer cell line with a species of origin Mus musculus

View all literature mentions

HUVEC-C (tool)

RRID:CVCL_2959

Cell line HUVEC-C is a Finite cell line with a species of origin Homo sapiens

View all literature mentions

HUVEC-C (tool)

RRID:CVCL_2959

Cell line HUVEC-C is a Finite cell line with a species of origin Homo sapiens

View all literature mentions