# Tenancin-C as a major component of the fibrogenic niche

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $393,524

## Abstract

Summary/abstract
 Tubulointerstitial fibrosis, a common endpoint outcome of a wide range of chronic kidney
diseases (CKD), typically initiates at certain focal sites, in which interstitial fibroblasts become
activated, proliferate and produce a large amount of extracellular matrix. This competitive renewal
application proposes to delineate the role of tenascin C (TNC), a matricellular protein, in orchestrating
the formation of fibrogenic microenvironment in kidney fibrosis. Studies in previous project period of
this application indicate that TNC is induced rapidly in the early stage of kidney injury and
predominantly localizes at the foci rich in fibroblasts. TNC is able to promote renal interstitial
fibroblast proliferation in vitro, ex vivo and in vivo. Intriguingly, TNC binds to, recruits and
concentrates sonic hedgehog (Shh) and Wnt ligands from surrounding milieu. Based on these
observations, the central hypothesis of this application is that TNC organizes a profibrotic
microenvironment in which Shh and Wnts are enriched, thereby setting a unique stage
facilitating fibroblast activation and proliferation, as well as aggravating tubular injury and
inflammation. We will test this hypothesis in three specific aims. Aim 1 is to investigate the role of
TNC in establishing fibrogenic microenvironment by recruiting, concentrating and presenting Wnt and
Shh ligands. Aim 2 is to investigate the role of injured tubules and activated macrophages in building
the fibrogenic niche, and to investigate the role of TNC-rich niche in aggravating tubular injury and
inflammation. Aim 3 is to evaluate the therapeutic efficiency of disrupting TNC-enriched
microenvironment for treatment of fibrotic CKD. These studies promise to offer novel insights into
understanding the role of TNC in organizing a profibrotic microenvironment. The concept that the
TNC-rich microenvironment, in which fibrotic factors are recruited and enriched, plays a critical role in
renal fibrogenesis represents a new paradigm in our understanding of kidney fibrosis. Undoubtedly,
the data generated from this application will have wide implications in comprehending the
pathogenesis of tissue fibrosis in general and kidney fibrosis in particular, as well as in designing
future therapeutic regimens for treatment.

## Key facts

- **NIH application ID:** 9971522
- **Project number:** 5R01DK064005-15
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** YOUHUA LIU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $393,524
- **Award type:** 5
- **Project period:** 2003-05-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971522

## Citation

> US National Institutes of Health, RePORTER application 9971522, Tenancin-C as a major component of the fibrogenic niche (5R01DK064005-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9971522. Licensed CC0.

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