Serum α-SMA is a potential noninvasive biomarker of liver fibrosis

Abstract

The severity of fibrosis is central to the therapeutic course for patients with chronic liver disease; therefore, early detection of liver fibrosis is critical for timely therapeutic interventions. Liver biopsy is the gold standard for the diagnosis of liver fibrosis; however, it is contraindicated in several pathological conditions. Activated hepatic stellate cells (HSCs) are the main cells for fibrotic tissue synthesis, such as that of alpha-smooth muscle actin (α-SMA). This study aimed to determine whether serum α-SMA levels are a suitable noninvasive, sensitive, and reliable liver fibrosis marker. Fibrosis was induced in male Wistar rats via chronic CCl₄ administration. Fibrosis was determined in the liver tissues by quantifying the hydroxyproline content and visualized using Masson’s trichrome staining. Rats chronically administered CCl₄ exhibited a progressive increment in the hepatic collagen content, as well as both hepatic and serum α-SMA levels in a time-dependent manner. Moreover, serum levels of α-SMA significantly correlated with hepatic α-SMA levels (p ≤ 0.001), as well as with the severity of liver fibrosis (p ≤ 0.001). These findings suggest that increased levels of serum α-SMA can be considered a potential reliable and noninvasive biomarker for early liver fibrosis.

Keywords:

• Alpha-smooth muscle actin
• biomarker
• hepatic stellate cells
• extracellular matrix
• HSC

Acknowledgments

The authors thank Dr. Víctor-Tsutsumi, Laura Dayana Buendia Montaño, Rosa E. Flores Beltrán, Benjamín E. Chávez, Ricardo Gaxiola, Rafael Leyva, Karla M. Gil Becerril, Silvia Galindo Gómez, Iván Galván Mendoza and Dr. Fernado Enríquez Rincón for technical assistance. The authors also acknowledge the Animal Lab Facility to UPEAL- Cinvestav and Dr. Jorge Fernández-Hernández.

Author contributions

Conceptualization: ICL, JAR, VRVG, SVT, PM; Data curation: ICL, PM; Formal analysis: ICL, PM; Funding acquisition: JAR, VRVG, SVT, PM; Investigation: ICL, ER, PM; Methodology: EEVP, ER, JAR; Project administration: PM; Supervision: PM; Writing-original draft: ICL; Writing-review & editing: PM.

Ethical approval

The experimental protocol was approved by the institutional animal care and use committee of CINVESTAV-IPN and was registered under the number 207 − 16.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The dataset analyzed during this study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the National Council of Humanities, Science and Technology (Conahcyt) of Mexico (grant. 53358 to P. Muriel), and fellowship no. 762331 to Irina Cardoso-Lezama.