# The role TGF-beta Signaling pathway in microglia and astrocytes homeostasis and cellular interactions

> **NIH NIH R01** · UNIVERSITY OF CINCINNATI · 2024 · $509,077

## Abstract

Stroke is one of the leading causes of death and disability worldwide and places a heavy burden on the
economy in our society. Recently it has been recognized that ischemic stroke elicits a strong neuroinflammatory
response characterized by massive microglia and astrocytes activation and this excessive neuroinflammatory
response could affect the long-term outcome of stroke. The long-term goal of our lab is to understand key
components of the CNS that determine neuronal survival and neurorepair, to improve functional outcomes
from CNS injury or chronic neurological diseases. One of our research interests is to characterize how
microglia cells affect the function of astrocytes and eventually determines the survival of neurons under both
physiological and pathological conditions. TGF-β has recently been suggested as a key factor in the
maintenance of microglia homeostasis under physiological conditions in adult brain. However, its role
regulating injury-induced microglia and astrocyte responses during different stages of pathology development
has not been investigated. TGF-β pharmacological modulators (inhibitors and activators) have shown mixed
and conflicting results in stroke animal models, depending on the dosage and time of administration. These
findings emphasize the importance of precise temporal and cell type specific modulation of this pathway. To
precisely investigate the role of TGF-β signaling pathway in microglia maintenance and astrocyte crosstalk, we
have developed multiple cell-type specific and temporally inducible ligand or receptor conditional KO mice. Our
preliminary data indicates that TGF-β signaling is important in maintaining the resting CNS microglia signature
profile under physiological condition and ablation of TGF-β signaling in microglia not only prime microglia cells
to pre-inflammatory states, but also activate quiescent astrocytes. Utilizing novel inducible conditional KO mice
lines, we will test our central hypotheses that 1)TGF-β signaling is important in the homeostasis of microglia
function and its cross-talk with astrocytes under pathophysiological conditions and 2) that modulation of this
pathway will lead to altered CNS functional outcome. If successful, the knowledge that will be gained from this
proposal is not limited to stroke research but can also have broader impact on the role of TGF-β1 signaling in
neuroinflammation regulation and microglia-astrocyte crosstalk in other CNS diseases.

## Key facts

- **NIH application ID:** 10831457
- **Project number:** 5R01NS125074-03
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Yu Luo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $509,077
- **Award type:** 5
- **Project period:** 2022-05-15 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10831457

## Citation

> US National Institutes of Health, RePORTER application 10831457, The role TGF-beta Signaling pathway in microglia and astrocytes homeostasis and cellular interactions (5R01NS125074-03). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10831457. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*