ORIGINAL ARTICLE Overexpression of apoptosis-related protein, survivin, in fibroblasts from patients with systemic sclerosis Mohammad Bagher Mahmoudi 1,2 & Ehsan Farashahi Yazd 3 & Farhad Gharibdoost 2 & Mohammad Hasan Sheikhha 1,4 & Elham Karimizadeh 2 & Ahmadreza Jamshidi 2 & Mahdi Mahmoudi 2 Received: 13 October 2018 /Accepted: 29 January 2019 # Royal Academy of Medicine in Ireland 2019 Abstract Background/objectives Recent studies suggest that, in addition to activation and hypersecretion of matrix components, fibro- blasts from patients with systemic sclerosis (SSc) are resistant to apoptosis. Previous studies have shown that survivin, a member of inhibition of apoptosis (IAP) family, plays an important role in apoptosis resistance. Accordingly, we decided to study the expression of the most important members of IAP family in SSc fibroblasts, which can block apoptosis either by binding and inhibiting caspases or through caspase-independent mechanisms. Method Skin biopsy samples were obtained from 19 patients with diffuse cutaneous SSc (DcSSc) and 16 healthy controls. Dermal fibroblasts were cultured and the total RNA was isolated from cells followed by cDNA synthesis. Real-time PCR was performed using SYBR Green PCR master mix and specific primers for cIAP1, cIAP2, XIAP , and Survivin mRNA quantification. Results A significantly increased expression level of Survivin was observed in fibroblasts from SSc patients compared to controls (2.26-fold, P = 0.04). However, mRNA expression of cIAP1, cIAP2, and XIAP did not change significantly between cases and controls. Conclusions Our results showed that survivin is upregulated in SSc skin fibroblast which may lead to resistance to apoptosis. Further studies should be performed to reveal the role of survivin in apoptosis pathway of SSc fibroblasts. Keywords Apoptosis . Fibroblast . IAP . Survivin . Systemic sclerosis Introduction Systemic sclerosis (SSc) is a slowly progressing connective tissue disorder, characterized by three major features, includ- ing vasculopathy, fibrosis, and inflammation [1]. SSc is a multifactorial disorder and both genetics and environmental risk factors predispose individuals to disease [2–5]. Fibrosis, the hallmark of SSc, is featured as an increased deposition of the extracellular matrix along with the destruction of normal tissue architecture, causing tissue and organ dysfunction [1, 6, 7]. The cultured fibroblasts isolated from sclerotic lesions of SSc patients preserve characteristics such as increased synthe- sis of collagen and other extracellular matrix components, proliferative behavior, and resistance to apoptosis. Therefore, therapeutic approaches of SSc have concentrated on apoptosis induction of fibroblasts [8–11]. Alternately, preserved charac- teristics of cultured SSc fibroblasts make them suitable exper- imental models for studying the mechanisms involved in over- production of the extracellular matrix and apoptosis resistance in SSc [12]. The inhibitor of apoptosis (IAP) family proteins is distin- guished by Baculovirus IAP Repeat (BIR) and able to sup- press apoptosis [13–15]. Three major determinants involved in the apoptosis progress are IAPs, IAP antagonists, and caspases [16]. IAPs are endogenous inhibitors of caspases, which are the main players of apoptosis. IAPs can also restrain the caspases via ubiquitination process. In addition to * Farhad Gharibdoost f_gharibdoost@hotmail.com * Mahdi Mahmoudi mahmoudim@tums.ac.ir 1 Department of Genetics, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 2 Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran 3 Stem Cell Biology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 4 Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Irish Journal of Medical Science (1971 -) https://doi.org/10.1007/s11845-019-01978-w