Direct trafficking pathways from the Golgi apparatus to the plasma membrane.

In eukaryotic cells, protein sorting is a highly regulated mechanism important for many physiological events. After synthesis in the endoplasmic reticulum and trafficking to the Golgi apparatus, proteins sort to many different cellular destinations including the endolysosomal system and the extracellular space. Secreted proteins need to be delivered directly to the cell surface. Sorting of secreted proteins from the Golgi apparatus has been a topic of interest for over thirty years, yet there is still no clear understanding of the machinery that forms the post-Golgi carriers. Most evidence points to these post-Golgi carriers being tubular pleomorphic structures that bud from the trans-face of the Golgi. In this review, we present the background studies and highlight the key components of this pathway, we then discuss the machinery implicated in the formation of these carriers, their translocation across the cytosol, and their fusion at the plasma membrane.

Protein Kinases Signaling in Pancreatic Beta-cells Death and Type 2 Diabetes.

Type 2 diabetes (T2D) is a worldwide serious public health problem. Insulin resistance and ß-cell failure are the two major components of T2D pathology. In addition to defective endoplasmic reticulum (ER) stress signaling due to glucolipotoxicity, ß-cell dysfunction or ß-cell death initiates the deleterious vicious cycle observed in T2D. Although the primary cause is still unknown, overnutrition that contributes to the induction of the state of low-grade inflammation, and the activation of various protein kinases-related metabolic pathways are main factors leading to T2D. In this chapter following subjects, which have critical checkpoints regarding ß-cell fate and protein kinases pathways are discussed; hyperglycemia-induced ß-cell failure, chronic accumulation of unfolded protein in ß-cells, the effect of intracellular reactive oxygen species (ROS) signaling to insulin secretion, excessive saturated free fatty acid-induced ß-cell apoptosis, mitophagy dysfunction, proinflammatory responses and insulin resistance, and the reprogramming of ß-cell for differentiation or dedifferentiation in T2D. There is much debate about selecting proposed therapeutic strategies to maintain or enhance optimal ß-cell viability for adequate insulin secretion in T2D. However, in order to achieve an effective solution in the treatment of T2D, more intensive clinical trials are required on newer therapeutic options based on protein kinases signaling pathways.

Effect of lifelong carnitine supplementation on plasma and tissue carnitine status, hepatic lipid metabolism and stress signalling pathways and skeletal muscle transcriptome in mice at advanced age.

While strong evidence from clinical studies suggests beneficial effects of carnitine supplementation on metabolic health, serious safety concerns associated with carnitine supplementation have been raised from studies in mice. Considering that the carnitine doses in these mice studies were up to 100 times higher than those used in clinical studies, the present study aimed to address possible safety concerns associated with long-term supplementation of a carnitine dose used in clinical trials. Two groups of NMRI mice were fed either a control or a carnitine-supplemented diet (1 g/kg diet) from weaning to 19 months of age, and parameters of hepatic lipid metabolism and stress signalling and skeletal muscle gene expression were analysed in the mice at 19 months of age. Concentrations of free carnitine and acetylcarnitine in plasma and tissues were higher in the carnitine than in the control group (P<0·05). Plasma concentrations of free carnitine and acetylcarnitine were higher in mice at adult age (10 and 15 months) than at advanced age (19 months) (P<0·05). Hepatic mRNA and protein levels of genes involved in lipid metabolism and stress signalling and hepatic and plasma lipid concentrations did not differ between the carnitine and the control group. Skeletal muscle transcriptome analysis in 19-month-old mice revealed only a moderate regulation between carnitine and control group. Lifelong carnitine supplementation prevents an age-dependent impairment of plasma carnitine status, but safety concerns associated with long-term supplementation of carnitine at doses used in clinical trials can be considered as unfounded.

The importance of phospholipids combined with long-chain PUFA in formulated diets for pikeperch (Sander lucioperca) larvae.

Dietary phosphoglycerides and n-3 long-chain PUFA (LC-PUFA) play important functions in the development of pikeperch (Sander lucioperca) larvae. This study aimed to determine optimal dietary levels of soyabean lecithin (SBL)-derived phospholipids (PL) in starter feeds for pikeperch larvae 10-30 d post-hatch (DPH) and examine performance and ontogeny by additional supplementation of n-3 LC-PUFA in the form of Algatrium DHA 70 (glyceride product; 660-700 mg/g DHA; EPA 60-75 mg/g). In total, six isoproteic and isoenergetic extruded diets were formulated with increasing levels of PL (3·7, 8·3 or 14·5 % wet weight (w.w.), respectively); however, three of the diets were supplemented with three levels of Algatrium DHA 70 (0·6, 2·0 or 3·4 %, respectively). Liver proteomic analyses of larvae at 30 DPH were included for effects of PL and primarily DHA on performance, physiological expression and interactions in larval proteins. In addition, bone anomalies, digestive enzymatic activity, candidate gene expression and skeleton morphogenesis were examined. Results confirmed the importance of dietary PL levels of at least 8·2 % w.w., and an additional beneficiary effect of supplementation with DHA plus EPA. Thus, combined supplementation of SBL (up to 14·51 % w.w. PL) and n-3 LC-PUFA (1·004 % DM DHA and 0·169 % DM EPA) in the form of TAG resulted in highest growth and lowest incidence of anomalies, improved digestive enzyme activity and had differential effect on liver proteomics. The results denote that essential fatty acids can be supplemented as TAG to have beneficial effects in pikeperch larvae development.

Biosynthesis of galactomannans found in filamentous fungi belonging to Pezizomycotina.

The galactomannans (GMs) that are produced by filamentous fungi belonging to Pezizomycotina, many of which are pathogenic for animals and plants, are polysaccharides consisting of α-(1→2)-/α-(1→6)-mannosyl and ß-(1→5)-/ß-(1→6)-galactofuranosyl residues. GMs are located at the outermost layer of the cell wall. When a pathogenic fungus infects a host, its cell surface must be in contact with the host. The GMs on the cell surface may be involved in the infection mechanism of a pathogenic fungus or the defense mechanism of a host. There are two types of GMs in filamentous fungi, fungal-type galactomannans and O-mannose type galactomannans. Recent biochemical and genetic advances have facilitated a better understanding of the biosynthesis of both types. This review summarizes our current information on their biosynthesis.

Regulation of intracellular trafficking and secretion of adiponectin by myosin II.

Adiponectin is a protein secreted by white adipocytes that plays an important role in insulin action, energy homeostasis and the development of atherosclerosis. The intracellular localization and trafficking of GLUT4 and leptin in adipocytes has been well studied, but little is known regarding the intracellular trafficking of adiponectin. Recent studies have demonstrated that constitutive adiponectin secretion is dependent on PIP2 levels and the integrity of cortical F-actin. Non-muscle myosin II is an actin-based motor that is associated with membrane vesicles and participates in vesicular trafficking in mammalian cells. Therefore, we investigated the role of myosin II in the trafficking and secretion of adiponectin in 3T3-L1 adipocytes. Confocal microscopy revealed that myosin IIA and IIB were dispersed throughout the cytoplasm of the adipocyte. Both myosin isoforms were localized in the Golgi/TGN region as evidenced by colocalization with the cis-Golgi marker, p115 and the trans-Golgi marker, γ-adaptin. Inhibition of myosin II activity by blebbistatin or actin depolymerization by latrunculin B dispersed myosin IIA and IIB towards the periphery while significantly inhibiting adiponectin secretion. Therefore, the constitutive trafficking and secretion of adiponectin in 3T3-L1 adipocytes occurs by an actin-dependent mechanism that involves the actin-based motors, myosin IIA and IIB.

Glycative Stress and Its Defense Machinery Glyoxalase 1 in Renal Pathogenesis.

Chronic kidney disease is a major public health problem around the world. Because the kidney plays a role in reducing glycative stress, renal dysfunction results in increased glycative stress. In turn, glycative stress, especially that due to advanced glycated end products (AGEs) and their precursors such as reactive carbonyl compounds, exacerbates chronic kidney disease and is related to premature aging in chronic kidney disease, whether caused by diabetes mellitus or otherwise. Factors which hinder a sufficient reduction in glycative stress include the inhibition of anti-glycation enzymes (e.g., GLO-1), as well as pathogenically activated endoplasmic reticulum (ER) stress and hypoxia in the kidney. Promising strategies aimed at halting the vicious cycle between chronic kidney disease and increases in glycative stress include the suppression of AGE accumulation in the body and the enhancement of GLO-1 to strengthen the host defense machinery against glycative stress.

Weight loss-induced stress in subcutaneous adipose tissue is related to weight regain.

Initial successful weight loss is often followed by weight regain after the dietary intervention. Compared with lean people, cellular stress in adipose tissue is increased in obese subjects. However, the relation between cellular stress and the risk for weight regain after weight loss is unclear. Therefore, we determined the expression levels of stress proteins during weight loss and weight maintenance in relation to weight regain. In vivo findings were compared with results from in vitro cultured human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes. In total, eighteen healthy subjects underwent an 8-week diet programme with a 10-month follow-up. Participants were categorised as weight maintainers or weight regainers (WR) depending on their weight changes during the intervention. Abdominal subcutaneous adipose tissue biopsies were obtained before and after the diet and after the follow-up. In vitro differentiated SGBS adipocytes were starved for 96 h with low (0·55 mm) glucose. Levels of stress proteins were determined by Western blotting. WR showed increased expressions of ß-actin, calnexin, heat shock protein (HSP) 27, HSP60 and HSP70. Changes of ß-actin, HSP27 and HSP70 are linked to HSP60, a proposed key factor in weight regain after weight loss. SGBS adipocytes showed increased levels of ß-actin and HSP60 after 96 h of glucose restriction. The increased level of cellular stress proteins in the adipose tissue of WR probably resides in the adipocytes as shown by in vitro experiments. Cellular stress accumulated in adipose tissue during weight loss may be a risk factor for weight regain.

The role of rumen-protected choline in hepatic function and performance of transition dairy cows.

High-producing dairy cows enter a period of negative energy balance during the first weeks of lactation. Energy intake is usually sufficient to cover the increase in energy requirements for fetal growth during the period before calving, but meeting the demand for energy is often difficult during the early stages of lactation. A catabolic state predominates during the transition period, leading to the mobilisation of energy reserves (NEFA and amino acids) that are utilised mainly by the liver and muscle. Increased uptake of mobilised NEFA by the liver, combined with the limited capacity of hepatocytes to either oxidise fatty acids for energy or to incorporate esterified fatty acids into VLDL results in fatty liver syndrome and ketosis. This metabolic disturbance can affect the general health, and it causes economic losses. Different nutritional strategies have been used to restrict negative effects associated with the energy challenge in transition cows. The provision of choline in the form of rumen-protected choline (RPC) can potentially improve liver function by increasing VLDL exportation from the liver. RPC increases gene expression of microsomal TAG transfer protein and APOB100 that are required for VLDL synthesis and secretion. Studies with RPC have looked at gene expression, metabolic hormones, metabolite profiles, milk production and postpartum reproduction. A reduction in liver fat and enhanced milk production has been observed with RPC supplementation. However, the effects of RPC on health and reproduction are equivocal, which could reflect the lack of sufficient dose-response studies.

Reversibility of endothelial dysfunction in diabetes: role of polyphenols.

The endothelium, a thin single sheet of endothelial cells, is a metabolically active layer that coats the inner surface of blood vessels and acts as an interface between the circulating blood and the vessel wall. The endothelium through the secretion of vasodilators and vasoconstrictors serves as a critical mediator of vascular homeostasis. During the development of the vascular system, it regulates cellular adhesion and vessel wall inflammation in addition to maintaining vasculogenesis and angiogenesis. A shift in the functions of the endothelium towards vasoconstriction, proinflammatory and prothrombic states characterise improper functioning of these cells, leading to endothelial dysfunction (ED), implicated in the pathogenesis of many diseases including diabetes. Major mechanisms of ED include the down-regulation of endothelial nitric oxide synthase levels, differential expression of vascular endothelial growth factor, endoplasmic reticulum stress, inflammatory pathways and oxidative stress. ED tends to be the initial event in macrovascular complications such as coronary artery disease, peripheral arterial disease, stroke and microvascular complications such as nephropathy, neuropathy and retinopathy. Numerous strategies have been developed to protect endothelial cells against various stimuli, of which the role of polyphenolic compounds in modulating the differentially regulated pathways and thus maintaining vascular homeostasis has been proven to be beneficial. This review addresses the factors stimulating ED in diabetes and the molecular mechanisms of natural polyphenol antioxidants in maintaining vascular homeostasis.

Arabinogalactan proteins - Multifunctional glycoproteins of the plant cell wall.

Arabinogalactan-proteins (AGPs) are cell wall glycoproteins that make up a relatively small component of the extracellular matrix of plants yet have significant influence on wall mechanics and signalling. Present in walls of algae, bryophytes and angiosperms, AGPs have a wide range of functional roles, from signalling, cell expansion and division, embryogenesis, responses to abiotic and biotic stress, plant growth and development. AGPs interact with and influence wall matrix components and plasma membrane proteins to regulate developmental pathways and growth responses, yet the exact mechanisms remain elusive. Comprising a large gene family that is highly diverse, from minimally to highly glycosylated members, varying in their glycan heterogeneity, can be plasma membrane bound or secreted into the extracellular matrix, have members that are highly tissue specific to those with constitutive expression; all these factors have made it extremely challenging to categorise AGPs many qualities and roles. Here we attempt to define some key features of AGPs and their biological functions.

Adipocytes in obesity: A perfect reservoir for SARS-CoV-2?

Research evidence suggests that adipocytes in obesity might facilitate SARS-CoV-2 replication, for it was only found in adipose tissue of individuals with overweight or obesity but not lean individuals who died from COVID-19. As lipid metabolism is key to adipocyte function, and viruses are capable of exploiting and manipulating lipid metabolism of host cells for their own benefit of infection, we hypothesize that adipocytes could not only impair host immune defense against viral infection, but also facilitate SARS-CoV-2 entry, replication and assembly as a reservoir to boost the viral infection in obesity. The latter of which could mainly be mediated by SARS-CoV-2 hijacking the abnormal lipid metabolism in the adipocytes. If these were to be confirmed, an approach to combat COVID-19 in people with obesity by taking advantage of the abnormal lipid metabolism in adipocytes might be considered, as well as modifying lipid metabolism of other host cells as a potential adjunctive treatment for COVID-19.

Trans-scale thermal signaling in biological systems.

Biochemical reactions in cells serve as the endogenous source of heat, maintaining a constant body temperature. This process requires proper control; otherwise, serious consequences can arise due to the unwanted but unavoidable responses of biological systems to heat. This review aims to present a range of responses to heat in biological systems across various spatial scales. We begin by examining the impaired thermogenesis of malignant hyperthermia in model mice and skeletal muscle cells, demonstrating that the progression of this disease is caused by a positive feedback loop between thermally driven Ca2+ signaling and thermogenesis at the subcellular scale. After we explore thermally driven force generation in both muscle and non-muscle cells, we illustrate how in vitro assays using purified proteins can reveal the heat-responsive properties of proteins and protein assemblies. Building on these experimental findings, we propose the concept of 'trans-scale thermal signaling'.

Hepatitis C virus replication requires integrity of mitochondria-associated ER membranes.

Background & Aims: Chronic HCV infection causes cellular stress, fibrosis and predisposes to hepatocarcinogenesis. Mitochondria play key roles in orchestrating stress responses by regulating bioenergetics, inflammation and apoptosis. To better understand the role of mitochondria in the viral life cycle and disease progression of chronic hepatitis C, we studied morphological and functional mitochondrial alterations induced by HCV using productively infected hepatoma cells and patient livers. Methods: Biochemical and imaging assays were used to assess localization of cellular and viral proteins and mitochondrial functions in cell cultures and liver biopsies. Cyclophilin D (CypD) knockout was performed using CRISPR/Cas9 technology. Viral replication was quantified by quantitative reverse-transcription PCR and western blotting. Results: Several HCV proteins were found to associate with mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), the points of contact between the ER and mitochondria. Downregulation of CypD, which is known to disrupt MAM integrity, reduced viral replication, suggesting that MAMs play an important role in the viral life cycle. This process was rescued by ectopic CypD expression. Furthermore, HCV proteins were found to associate with voltage dependent anion channel 1 (VDAC1) at MAMs and to reduce VDAC1 protein levels at MAMs in vitro and in patient biopsies. This association did not affect MAM-associated functions in glucose homeostasis and Ca2+ signaling. Conclusions: HCV proteins associate specifically with MAMs and MAMs play an important role in viral replication. The association between viral proteins and MAMs did not impact Ca2+ signaling between the ER and mitochondria or glucose homeostasis. Whether additional functions of MAMs and/or VDAC are impacted by HCV and contribute to the associated pathology remains to be assessed. Impact and implications: Hepatitis C virus infects the liver, where it causes inflammation, cell damage and increases the long-term risk of liver cancer. We show that several HCV proteins interact with mitochondria in liver cells and alter the composition of mitochondrial subdomains. Importantly, HCV requires the architecture of these mitochondrial subdomains to remain intact for efficient viral replication.

Polysaccharides from Panax ginseng promote intestinal epithelial cell migration through affecting the Ca2+ related regulators.

Background and aim: Panax ginseng, a key herbal medicine of replenishing Qi and tonifying Spleen, is widely used in the treatment of gastrointestinal diseases in East Asia. In this study, we aim to investigate the potential effects and mechanisms of polysaccharides from P. ginseng (PGP) on intestinal mucosal restitution which is one of the crucial repair modalities during the recovery of mucosal injury controlled by the Ca2+ signaling. Methods: Rat model of intestinal mucosal injury was induced by indomethacin. The fractional cell migration was carried out by immunohistochemistry staining with BrdU. The morphological observations on intestinal mucosal injury were also performed. Intestinal epithelial cell (IEC-6) migration in vitro was conducted by scratch method. Western-blot was adopted to determine the expressions of PLC-γ1, Rac1, TRPC1, RhoA and Cav-1. Immunoprecipitation was used to evaluate the levels of Rac1/PLC-γ1, RhoA/TRPC1 and Cav-1/TRPC1. Results: The results showed that PGP effectively reduced the assessment of intestinal mucosal injury, reversed the inhibition of epithelial cell migration induced by Indomethacin, and increased the level of Ca2+ in intestinal mucosa in vivo. Moreover, PGP dramatically promoted IEC-6 cell migration, the expression of Ca2+ regulators (PLC-γ1, Rac1, TRPC1, Cav-1 and RhoA) as well as protein complexes (Rac1/PLC-γ1, Cav-1/TRPC1 and RhoA/TRPC1) in vitro. Conclusion: PGP increases the Ca2+ content in intestinal mucosa partly through controlling the regulators of Ca2+ mobilization, subsequently promotes intestinal epithelial cell migration, and then prevents intestinal mucosal injury induced by indomethacin.

A lipid scramblase TMEM41B is involved in the processing and transport of GPI-anchored proteins.

Protein modification by glycosylphosphatidylinositol (GPI) takes place in the endoplasmic reticulum (ER). GPI-anchored proteins (GPI-APs) formed in the ER are transported to the cell surface through the Golgi apparatus. During transport, the GPI-anchor structure is processed. In most cells, an acyl chain modified to the inositol of GPI is removed by a GPI-inositol deacylase, PGAP1, in the ER. Inositol-deacylated GPI-APs become sensitive to bacterial phosphatidylinositol-specific phospholipase C (PI-PLC). We previously reported that GPI-APs are partially resistant to PI-PLC when PGAP1 activity is weakened by the deletion of selenoprotein T (SELT) or cleft lip and palate transmembrane protein 1 (CLPTM1). In this study, we found that the loss of TMEM41B, an ER-localized lipid scramblase, restored PI-PLC sensitivity of GPI-APs in SELT-knockout (KO) and CLPTM1-KO cells. In TMEM41B-KO cells, the transport of GPI-APs as well as transmembrane proteins from the ER to the Golgi was delayed. Furthermore, the turnover of PGAP1, which is mediated by ER-associated degradation, was slowed in TMEM41B-KO cells. Taken together, these findings indicate that inhibition of TMEM41B-dependent lipid scrambling promotes GPI-AP processing in the ER through PGAP1 stabilization and slowed protein trafficking.

Dermatologic Manifestations of Noninflammasome-Mediated Autoinflammatory Diseases.

Autoinflammatory diseases (AIDs) arise from disturbances that alter interactions of immune cells and tissues. They give rise to prominent (auto)inflammation in the absence of aberrant autoantibodies and/or autoreactive T cells. AIDs that are predominantly caused by changes in the inflammasome pathways, such as the NLRP3- or pyrin-associated inflammasome, have gained substantial attention over the last years. However, AIDs resulting primarily from other changes in the defense system of the innate immune system are less well-studied. These noninflammasome-mediated AIDs relate to, for example, disturbance in the TNF or IFN signaling pathways or aberrations in genes affecting the IL-1RA. The spectrum of clinical signs and symptoms of these conditions is vast. Thus, recognizing early cutaneous signs constitutes an important step in differential diagnoses for dermatologists and other physicians. This review provides an overview of the pathogenesis, clinical presentation, and available treatment options highlighting dermatologic aspects of noninflammasome-mediated AIDs.

Jaw1/LRMP is associated with the maintenance of Golgi ribbon structure.

Jaw1/LRMP is a membrane protein that is localized to the endoplasmic reticulum and outer nuclear membrane. Previously, we revealed that Jaw1 functions to maintain nuclear shape by interacting with microtubules as a Klarsicht/ANC-1/Syne/homology (KASH) protein. The loss of several KASH proteins causes defects in the position and shape of the Golgi apparatus as well as the nucleus, but the effects of Jaw1 depletion on the Golgi apparatus were poorly understood. Here, we found that siRNA-mediated Jaw1 depletion causes Golgi fragmentation with disordered ribbon structure in the melanoma cell, accompanied by the change in the localization of the Golgi-derived microtubule network. Thus, we suggest that Jaw1 is a novel protein to maintain the Golgi ribbon structure, associated with the microtubule network.

Impact of hematopoietic stem cell transplantation in glycogen storage disease type Ib: A single-subject research design using 13C-glucose breath test.

Background: Glycogen storage disease type Ib (GSD Ib) is an autosomal recessively inherited deficiency of the glucose-6-phosphate translocase (G6PT). Clinical features include a combination of a metabolic phenotype (fasting hypoglycemia, lactic acidosis, hepatomegaly) and a hematologic phenotype with neutropenia and neutrophil dysfunction. Dietary treatment involves provision of starches such as uncooked cornstarch (UCCS) and Glycosade® to provide prolonged enteral supply of glucose. Granulocyte colony-stimulating factor (G-CSF) is the treatment of choice for neutropenia. Because long-term stimulation of hematopoiesis with G-CSF causes serious complications such as splenomegaly, hypersplenism, and osteopenia; hematopoietic stem cell transplantation (HSCT) has been considered in some patients with GSD Ib to correct neutropenia and avoid G-CSF related adverse effects. Whether HSCT also has an effect on the metabolic phenotype and utilization of carbohydrate sources has not been determined. Objective: Our objective was to measure the utilization of starch in a patient with GSD Ib before and after HSCT using the minimally invasive 13C-glucose breath test (13C-GBT). Design: A case of GSD Ib (18y; female) underwent 13C-GBT four times: UCCS (pre-HSCT), UCCS (3, 5 months post-HSCT) and Glycosade® (6 months post-HSCT) with a dose of 80 g administered via nasogastric tube after a 4 h fast according to our patient's fasting tolerance. Breath samples were collected at baseline and every 30 min for 240 min. Rate of CO2 production was measured at 120 min using indirect calorimetry. Finger-prick blood glucose was measured using a glucometer hourly to test hypoglycemia (glucose <4 mmol/L). Biochemical and clinical data were obtained from the medical records as a post-hoc chart review. Results: UCCS utilization was significantly higher in GSD Ib pre-HSCT, which reduced and stabilized 5 months post-HSCT. UCCS and Glycosade® utilizations were low and not different at 5 and 6 months post-HSCT. Blood glucose concentrations were not significantly different at any time point. Conclusions: Findings show that HSCT stabilized UCCS utilization, as reflected by lower and stable glucose oxidation. The results also illustrate the application of 13C-GBT to examine glucose metabolism in response to various carbohydrate sources after other treatment modalities like HSCT in GSD Ib.

FAM172A supervises ER (endoplasmic reticulum) stress-triggered autophagy in the epidural fibrosis process.

Backgrounds: Lumbar laminectomy is usually utilized for lumbar disc herniation (LDH), but also causes epidural fibrosis (EF) process associated with abnormal proliferation of fibroblasts. FAM172A is associated with ER stress and cell proliferation, but its mechanism was unclear, especially in the process of EF. Methods: Therefore, the regulation of FAM172A on the calcium flux and autophagy in fibroblasts were investigated by inducing ER stress with tunicamycin and upexpression or downexpression of FAM172A. The calcium flux was determined using Fluo-3, and autophagy was examined with immunofluorescence or western blot for LC3, Beclin-1, ATG-5, and p62. Moreover, the apoptotic protein of Bax and Bcl-2 was detected, too. Furthermore, the laminectomy model was constructed and then dealt with overexpression of FAM172A. Results: Tunicamycin-induced endoplasmic reticulum (ER) stress and autophagy process in fibroblasts were associated with the calcium flux regulated by FAM172A, especially in EF cells. Besides, tunicamycin induced autophagy and suppressed cell apoptosis of fibroblasts. Furthermore, FAM72A repressed the proliferation of fibroblasts and the process of EF in the laminectomy model through the mediation of the autophagy process. Conclusions: Tunicamycin-induced endoplasmic reticulum (ER) stress in fibroblasts was associated with calcium flux mediated by FAM172A. FAM72A participated in the autophagy regulation of fibroblasts and maybe the key interaction regulator of apoptosis and autophagy in fibroblasts, especially for epidural scar cells.