Progesterone Aggravates Lung Fibrosis in a Mouse Model of Systemic Sclerosis.

Fatemeh Vafashoar,Salar Pashangzadeh,Amir Haghighi,Hadi Poormoghim,Kazem Mousavizadeh,Nazanin Mojtabavi

doi:10.3389/fimmu.2021.742227

Abstract

BackgroundGender-related factors have explained the higher prevalence of autoimmune diseases in women. Sex hormones play a key role in the immune system and parenchymal cells function; therefore, these hormones can be important in the pathogenesis of autoimmune diseases as a risk or beneficial factor. Lung fibrosis is the main cause of mortality in systemic sclerosis, a female predominant autoimmune disease. The objective of this study was to examine the effect of progesterone on lung fibrosis in a mouse model of systemic sclerosis.MethodsMice with bleomycin-induced lung fibrosis treated with progesterone subcutaneously for 21 and 28 days. Blood was collected for hormone and cytokine measurement at the end of treatment then, skin and lung tissues were harvested for histological assessment, gene expression, cytokine, hydroxyproline, and gelatinase measurement.ResultsTrichrome staining and hydroxyproline measurements showed that progesterone treatment increased the content of collagen in fibrotic and normal lung tissues. Progesterone increased α-SMA (P < 0.01), TGF- β (P < 0.05) and decreased MMP9 (P < 0.05) in fibrotic lung tissues. Also progesterone treatment decreased the gene expression of Col1a2 (P <0.05), Ctgf (P <01), End1 (0.001) in bleomycin- injured lung tissues. The serum level of TNF-α was decreased, but the serum level of cortisol was increased by progesterone treatment in fibrotic mice (P< 0.05).ConclusionOur results showed that progesterone aggravates lung fibrosis in a mouse model of systemic sclerosis.

Highlights

Systemic sclerosis (SSc) is a heterogeneous autoimmune disease with inflammatory – fibrotic changes in skin and internal organs, especially lungs [1]
Trichrome staining and hydroxyproline measurements showed that progesterone treatment increased the content of collagen in fibrotic and normal lung tissues
Our results showed that progesterone aggravates lung fibrosis in a mouse model of systemic sclerosis

Summary

Introduction

Systemic sclerosis (SSc) is a heterogeneous autoimmune disease with inflammatory – fibrotic changes in skin and internal organs, especially lungs [1]. Lung fibrosis and hypertension are the main causes of morbidity and mortality in SSc [2]. As fundamental elements in fibrosis, myofibroblasts produce extracellular matrix (ECM), especially collagen type 1 and matrix metalloproteinases (MMPs). An imbalance between ECM production and degradation causes excessive deposition of ECM and fibrosis in organs [1]. Lung fibrosis is the main cause of mortality in systemic sclerosis, a female predominant autoimmune disease. The objective of this study was to examine the effect of progesterone on lung fibrosis in a mouse model of systemic sclerosis

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Conclusion