X

Forgot your Password

If you have forgotten your password, please enter your account email below and we will reset your password and email you the new password.

X

Login to SciCrunch

X

Register an Account

Delete Saved Search

Are you sure you want to delete this saved search?

NO

NIF LinkOut Portal

FILTERS

The ADPKD genes pkd1a/b and pkd2 regulate extracellular matrix formation.

Authors:
Mangos S, Lam PY, Zhao A, Liu Y, Mudumana S, Vasilyev A, Liu A, Drummond IA
Affiliation:
Journal:
Disease models & mechanisms

Abstract

Mutations in polycystin1 (PKD1) account for the majority of autosomal dominant polycystic kidney disease (ADPKD). PKD1 mutations are also associated with vascular aneurysm and abdominal wall hernia, suggesting a role for polycystin1 in extracellular matrix (ECM) integrity. In zebrafish, combined knockdown of the PKD1 paralogs pkd1a and pkd1b resulted in dorsal axis curvature, hydrocephalus, cartilage and craniofacial defects, and pronephric cyst formation at low frequency (10-15%). Dorsal axis curvature was identical to the axis defects observed in pkd2 knockdown embryos. Combined pkd1a/b, pkd2 knockdown demonstrated that these genes interact in axial morphogenesis. Dorsal axis curvature was linked to notochord collagen overexpression and could be reversed by knockdown of col2a1 mRNA or chemical inhibition of collagen crosslinking. pkd1a/b- and pkd2-deficient embryos exhibited ectopic, persistent expression of multiple collagen mRNAs, suggesting a loss of negative feedback signaling that normally limits collagen gene expression. Knockdown of pkd1a/b also dramatically sensitized embryos to low doses of collagen-crosslinking inhibitors, implicating polycystins directly in the modulation of collagen expression or assembly. Embryos treated with wortmannin or LY-29400 also exhibited dysregulation of col2a1 expression, implicating phosphoinositide 3-kinase (PI3K) in the negative feedback signaling pathway controlling matrix gene expression. Our results suggest that pkd1a/b and pkd2 interact to regulate ECM secretion or assembly, and that altered matrix integrity may be a primary defect underlying ADPKD tissue pathologies.

GO Links

  1. Welcome

    Welcome to NIF. Explore available research resources: data, tools and materials, from across the web

  2. Community Resources

    Search for resources specially selected for NIF community

  3. More Resources

    Search across hundreds of additional biomedical databases

  4. Literature

    Search Pub Med abstracts and full text from PubMed Central

  5. Insert your Query

    Enter your search terms here and hit return. Search results for the selected tab will be returned.

  6. Join the Community

    Click here to login or register and join this community.

  7. Categories

    Narrow your search by selecting a category. For additional help in searching, view our tutorials.

  8. Query Info

    Displays the total number of search results. Provides additional information on search terms, e.g., automated query expansions, and any included categories or facets. Expansions, filters and facets can be removed by clicking on the X. Clicking on the + restores them.

  9. Search Results

    Displays individual records and a brief description. Click on the icons below each record to explore additional display options.

X