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Updated: Jul 22, 2025
Murine Dermal Fibroblast Isolation by FACS
Published on: January 7, 2016
GPCRs and fibroblast heterogeneity in fibroblast-associated diseases
Nidhi V Dwivedi1, Souvik Datta1, Karim El-Kersh2
1Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Abstract:
G protein-coupled receptors (GPCRs) are the largest and most diverse class of signaling receptors. GPCRs regulate many functions in the human body and have earned the title of "most targeted receptors". About one-third of the commercially available drugs for various diseases target the GPCRs. Fibroblasts lay the architectural skeleton of the body, and play a key role in supporting the growth, maintenance, and repair of almost all tissues by responding to the cellular cues via diverse and intricate GPCR signaling pathways. This review discusses the dynamic architecture of the GPCRs and their intertwined signaling in pathological conditions such as idiopathic pulmonary fibrosis, cardiac fibrosis, pancreatic fibrosis, hepatic fibrosis, and cancer as opposed to the GPCR signaling of fibroblasts in physiological conditions. Understanding the dynamics of GPCR signaling in fibroblasts with disease progression can help in the recognition of the complex interplay of different GPCR subtypes in fibroblast-mediated diseases. This review highlights the importance of designing and adaptation of next-generation strategies such as GPCR-omics, focused target identification, polypharmacology, and effective personalized medicine approaches to achieve better therapeutic outcomes for fibrosis and fibrosis associated malignancies.
Insights
G protein-coupled receptors (GPCRs) are crucial for fibroblast function in health and disease. This review explores GPCR signaling in fibrosis and cancer, advocating for advanced strategies to improve treatments.
Area of Science:
- Pharmacology
- Cell Biology
- Biochemistry
Background:
- G protein-coupled receptors (GPCRs) represent the largest receptor family, regulating numerous physiological functions.
- Approximately one-third of marketed drugs target GPCRs, highlighting their therapeutic significance.
- Fibroblasts utilize intricate GPCR signaling pathways to maintain tissue structure and repair.
Purpose of the Study:
- To review the dynamic architecture and signaling of GPCRs in fibroblasts.
- To contrast GPCR signaling in physiological fibroblast function with its role in pathological conditions like fibrosis and cancer.
- To emphasize the need for novel therapeutic strategies targeting GPCRs in fibroblast-mediated diseases.
Main Methods:
- Literature review focusing on GPCR signaling in fibroblast biology.
- Analysis of GPCR involvement in various fibrotic diseases (pulmonary, cardiac, pancreatic, hepatic) and cancer.
- Discussion of emerging therapeutic approaches, including GPCR-omics and personalized medicine.
Main Results:
- GPCR signaling dynamics in fibroblasts differ significantly between physiological and pathological states.
- Aberrant GPCR signaling in fibroblasts contributes to the pathogenesis of diverse fibrotic conditions and malignancies.
- Understanding GPCR subtype interplay is key to deciphering fibroblast-mediated diseases.
Conclusions:
- Fibroblast GPCR signaling is a critical determinant in fibrotic diseases and associated cancers.
- Next-generation strategies like GPCR-omics, polypharmacology, and personalized medicine offer promising therapeutic avenues.
- Targeting GPCRs in fibroblasts holds significant potential for improved treatment outcomes in fibrosis and cancer.
