# Cr(VI) exposure and skeletal muscle differentiation and regeneration

> **NIH NIH R56** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $548,707

## Abstract

SUMMARY
Hexavalent chromium, Cr(VI), is widely used in industrial processes such as stainless steel production,
electroplating, textile manufacturing, wood preservation, and leather tanning. Occupational or environmental
exposures to Cr(VI) have been associated with a variety of adverse respiratory, cardiovascular, gastrointestinal,
hematological, and hepatic effects. However, the impact of Cr(VI) exposure on musculoskeletal system is largely
unknown. The 3-month toxicity study by National Toxicology Program (NTP) reported a dose-related increase of
serum creatine kinase (CK) activities in rodents exposed to Cr(VI) via drinking water compared to the control
group, indicating muscle injury. Consistently, a significant increase of serum CK activity was reported in chrome
plating workers compared to the control subjects. Despite a clear sign of muscle injury has been reported in both
human and animal study, the impact of Cr(VI) exposure on muscle injury and regeneration is completely unknown.
Our preliminary study reveals that acute exposure of mouse C2C12 myoblast cells to Cr(VI) inhibits myogenic
differentiation in a dose-dependent manner. Additionally, Cr(VI) inhibition of myogenesis is further confirmed in
freshly isolated mouse primary myoblasts ex vivo. Moreover, the expression of key myogenic regulatory factors
(MRFs) was significantly altered in Cr(VI)-treated cells. Furthermore, whole transcriptome profiling using RNA-
sequencing identified many molecules and pathways that mediate Cr(VI) inhibition of myogenic differentiation.
Taking together, our results demonstrate an inhibitory effect of Cr(VI) in myogenic differentiation in vitro and ex
vivo. Given that in vitro myogenic differentiation largely recapitulates in vivo myogenesis during early embryo
development and adult muscle regeneration, we hypothesize that Cr(VI) adversely affects skeletal muscle
development and regeneration in vivo. In this proposal, we aim to address whether Cr(VI) lead to defective
myogenesis and impaired muscle regeneration with the following specific aims. First, we will examine the effects
of acute or chronic Cr(VI) exposure on adult muscle injury and regeneration in vivo. Second, we will explore the
impact of Cr(VI) on skeletal muscle development by assessing primary and secondary myogenesis in mouse
embryos prenatally exposed to Cr(VI). Lastly, to elucidate the mechanism underlying Cr(VI) inhibition of
myogenic differentiation, we will analyze the role of MyoD and Myf5 in Cr(VI)-induced defective myogenic
differentiation, and explore whether special AT-rich sequence-binding protein 2 (Satb2), a known Cr(VI) target
gene in lung carcinogenesis, acts as an important target or a functional mediator of Cr(VI) in myogenic
differentiation. The success of the proposed research will generate valuable evidence to support Cr(VI) exposure
as a risk factor for muscle impairment, and provide additional insights on prevention and therapeutic approaches
for muscle-related dis...

## Key facts

- **NIH application ID:** 11135847
- **Project number:** 1R56ES036591-01
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Hong Sun
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $548,707
- **Award type:** 1
- **Project period:** 2024-09-01 → 2025-08-21

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11135847

## Citation

> US National Institutes of Health, RePORTER application 11135847, Cr(VI) exposure and skeletal muscle differentiation and regeneration (1R56ES036591-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11135847. Licensed CC0.

---

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