Characterization of Matricellular Protein Expression Signatures in Mechanistically Diverse Mouse Models of Kidney Injury

Sci Rep. 2019 Nov 13;9(1):16736. doi: 10.1038/s41598-019-52961-5.

Abstract

Fibrosis is the most common pathophysiological manifestation of Chronic Kidney Disease (CKD). It is defined as excessive deposition of extracellular matrix (ECM) proteins. Embedded within the ECM are a family of proteins called Matricellular Proteins (MCPs), which are typically expressed during chronic pathologies for ECM processing. As such, identifying potential MCPs in the pathological secretome of a damaged kidney could serve as diagnostic/therapeutic targets of fibrosis. Using published RNA-Seq data from two kidney injury mouse models of different etiologies, Folic Acid (FA) and Unilateral Ureteral Obstruction (UUO), we compared and contrasted the expression profile of various members from well-known MCP families during the Acute and Fibrotic injury phases. As a result, we identified common and distinct MCP expression signatures between both injury models. Bioinformatic analysis of their differentially expressed MCP genes revealed similar top annotation clusters from Molecular Function and Biological Process networks, which are those commonly involved in fibrosis. Using kidney lysates from FA- and UUO-injured mice, we selected MCP genes from our candidate list to confirm mRNA expression by Western Blot, which correlated with injury progression. Understanding the expressions of MCPs will provide important insight into the processes of kidney repair, and may validate MCPs as biomarkers and/or therapeutic targets of CKD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Extracellular Matrix Proteins / metabolism*
  • Fibrosis / etiology
  • Fibrosis / metabolism*
  • Fibrosis / pathology
  • Folic Acid / toxicity
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Kidney Diseases / etiology
  • Kidney Diseases / metabolism*
  • Kidney Diseases / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Ureteral Obstruction / etiology
  • Ureteral Obstruction / metabolism*
  • Ureteral Obstruction / pathology
  • Vitamin B Complex / toxicity

Substances

  • Extracellular Matrix Proteins
  • Vitamin B Complex
  • Folic Acid