Extracellular Collagen VI Has Prosurvival and Autophagy Instructive Properties in Mouse Fibroblasts

Frontiers in Physiology
Silvia CastagnaroPaolo Bonaldo

Abstract

Collagen VI (ColVI) is an abundant and distinctive extracellular matrix protein secreted by fibroblasts in different tissues. Human diseases linked to mutations on ColVI genes are primarily affecting skeletal muscle due to non-cell autonomous myofiber defects. To date, it is not known whether and how fibroblast homeostasis is affected by ColVI deficiency, a critical missing information as this may strengthen the use of patients' fibroblasts for preclinical purposes. Here, we established primary and immortalized fibroblast cultures from ColVI null (Col6a1-/-) mice, the animal model of ColVI-related diseases. We found that, under nutrient-stringent condition, lack of ColVI affects fibroblast survival, leading to increased apoptosis. Moreover, Col6a1-/- fibroblasts display defects in the autophagy/lysosome machinery, with impaired clearance of autophagosomes and failure of Parkin-dependent mitophagy. Col6a1-/- fibroblasts also show an increased activation of the Akt/mTOR pathway, compatible with the autophagy impairment, and adhesion onto purified ColVI elicits a major effect on the autophagic flux. Our findings reveal that ColVI ablation in fibroblasts impacts on autophagy regulation and cell survival, thus pointing at the new co...Continue Reading

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Citations

Jul 8, 2020·Bioengineering·Weng Wan ChanMay Win Naing
Nov 3, 2020·Frontiers in Cell and Developmental Biology·Samuele MettiPaolo Bonaldo
Jan 10, 2021·Matrix Biology : Journal of the International Society for Matrix Biology·Kyle Sylakowski, Alan Wells
Jan 18, 2021·Matrix Biology : Journal of the International Society for Matrix Biology·Francis Migneault, Marie-Josée Hébert
Mar 16, 2021·Frontiers in Oncology·Maria Paz Hernández-CáceresCristina Bertocchi
Apr 11, 2021·Matrix Biology : Journal of the International Society for Matrix Biology·Thomas NeillRenato V Iozzo
Dec 30, 2020·Matrix Biology : Journal of the International Society for Matrix Biology·Silvia CastagnaroPaolo Bonaldo
Jul 5, 2021·Matrix Biology : Journal of the International Society for Matrix Biology·Liliana Schaefer, Ivan Dikic
Sep 3, 2021·Journal of Cell Science·Aurore Claude-TaupinNicolas Dupont
Sep 22, 2021·Blood Advances·Vittorio AbbonanteAlessandra Balduini

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Methods Mentioned

BETA
dissection
biopsies
Transfection
PCR
flow cytometry
Protein Assay
Fluorescence microscopy
lipidation
fluorescence
nuclear translocation

Software Mentioned

Flowing
GraphPad Prism
ImageJ
FACS Diva

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