# FGFR Signaling in Liver Injury and Fibrosis

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2023 · $429,133

## Abstract

ABSTRACT
 Liver fibrosis is a significant cause of mortality worldwide. Factors such as chronic liver
injury, infection, metabolic and toxin insults, and genetic factors are associated with the
development of liver fibrosis. Rapidly expanding intrahepatic biliary epithelium or ductular reaction
with a closely associated highly invasive bridging fibrosis are the characteristic features of
advanced liver fibrosis, which has no definite cure. Fibrosis leads to a significant distortion of
hepatic function, progresses to liver failure. Therefore, the prevention of fibrosis progression is of
paramount importance. Even after tremendous scientific advancements in the area of liver
fibrosis, the molecular and cellular mechanisms of how fibrosis progresses to an end-stage liver
disease remain a medical enigma. Previously we have shown that Fibroblast growth factor
receptors (FGFRs) were highly induced and co-localized to a heterogeneous population of biliary
precursors and profibrogenic cells co-expressing Prominin1 (PROM1) with an activated TGF beta
signaling in fibrotic livers. Based on the literature and preliminary studies, we hypothesize that
FGFRs via its crosstalk with the TGF beta pathway promotes ductular reaction and fibrosis in
chronically injured livers. The goals of this application are to elucidate the cell-type-specific role
of FGFRs in ductular reaction and fibrosis progression in a setting of chronic liver injury. Specific
aims of this proposal are: (1) Identify the mechanisms of FGFRs activation and its significance in
liver injury and fibrosis. (2) Elucidate the mechanism by which FGFR signaling in Prom1
expressing cells promote ductular reaction and fibrosis. (3) Identify the mechanism and the
significance of FGFR-TGF beta crosstalk in liver fibrosis. Successful completion of the proposed
work may identify novel therapeutic targets and FGFR-mediated signaling crosstalk that promotes
liver fibrosis progression during chronic liver injury.

## Key facts

- **NIH application ID:** 10640153
- **Project number:** 5R01DK131071-02
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Nirmala Mavila
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $429,133
- **Award type:** 5
- **Project period:** 2022-07-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10640153

## Citation

> US National Institutes of Health, RePORTER application 10640153, FGFR Signaling in Liver Injury and Fibrosis (5R01DK131071-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10640153. Licensed CC0.

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