Role Of Fibroblast Growth Factor Research Articles

Fibroblast growth factor 23 and its role in phosphate homeostasis in growing children compared to adults

Abstract Objectives Phosphate is essential for skeletal mineralization, which is regulated by parathyroid hormone, calcitriol and fibroblast growth factor 23 (FGF23). Serum phosphate is physiologically higher in younger children, but factors that contribute to this physiological state are poorly understood. This study aimed to evaluate phosphate and its regulators in children compared with adults. Materials and methods The participants were children aged 3–11 years and adults older than 20 years of age. Biochemical parameters including calcium, phosphorus, alkaline phosphatase, FGF23, and vitamin D were measured. Fractional excretion of phosphate was calculated, using serum and urine phosphate and creatinine. Results This cross-sectional study was conducted on 45 children (mean age: 9.0 ± 2.1) and 44 adults (mean age: 38.9 ± 11.1). The children had higher serum calcium, phosphate, alkaline phosphatase, and FGF23 (p < 0.001), but fractional excretion of phosphate was greater in adults (14.1 ± 5.7, 11.4 ± 4.4, p = 0.019, 95% confidence interval [CI]: −0.7 to −0.2). Of all individuals, 61.8% had vitamin D deficiency. By multiple regression analysis, entering age, calcium, phosphate, and vitamin D level, the only independent predictor of FGF23 was 1, 25 dihydroxy-vitamin D3 (β: 0.78, p < 0.001, 95% CI: 0.5–1.1, R2: 0.59 for children, and β: 0.59, p < 0.001, 95% CI: 0.5–1.4, R2: 0.45 for adults). Conclusion As far as we know, there is little information regarding the role of FGF23 in physiologic state. In this cross-sectional study no association was found between FGF23 and urinary phosphate excretion in growing children. Further studies with more detail are essential to evaluate phosphate homeostasis during childhood.

Targeting Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension (BPD-PH): Potential Role of the FGF Signaling Pathway in the Development of the Pulmonary Vascular System.

More than 50 years after the first description of Bronchopulmonary dysplasia (BPD) by Northway, this chronic lung disease affecting many preterm infants is still poorly understood. Additonally, approximately 40% of preterm infants suffering from severe BPD also suffer from Bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH), leading to a significant increase in total morbidity and mortality. Until today, there is no curative therapy for both BPD and BPD-PH available. It has become increasingly evident that growth factors are playing a central role in normal and pathologic development of the pulmonary vasculature. Thus, this review aims to summarize the recent evidence in our understanding of BPD-PH from a basic scientific point of view, focusing on the potential role of Fibroblast Growth Factor (FGF)/FGF10 signaling pathway contributing to disease development, progression and resolution.

Potential role of fibroblast growth factor 21 in the deterioration of bone quality in impaired glucose tolerance.

Findings on trabecular bone score (TBS), an index of bone quality, have been reported in prediabetes defined by impaired fasting glucose or HbA1c. Here, we assessed the bone mineral density (BMD) and TBS in prediabetes individuals with impaired glucose tolerance (IGT), and investigated the association of these bone parameters with serum levels of fibroblast growth factor 21 (FGF21), a hormone implicated in bone metabolism and with higher levels in IGT. Chinese postmenopausal women aged 55-80years, without diabetes, were recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study in 2016-2018. Normal glucose tolerance (NGT) was defined by fasting glucose < 5.6mmol/L and 2-h plasma glucose (2hG) < 7.8mmol/L, and IGT by 2hG 7.8-11mmol/L. Serum levels of FGF21 and other bone metabolism regulators were measured. Insulin sensitivity was assessed by the Matsuda index. Independent determinants of TBS were evaluated using multivariable stepwise linear regression. 173 individuals with NGT and 73 with IGT were included. TBS was lower in those with IGT compared to those with NGT, while BMD was comparable. Individuals with IGT had significantly higher serum FGF21 levels, which in turn showed an independent inverse relationship with TBS, attenuated after inclusion of the Matsuda index. Serum FGF21 levels, however, did not correlate with BMD. Among Chinese postmenopausal women, bone quality was worse in IGT, despite comparable bone density. FGF21 levels showed a significant independent inverse relationship with TBS, partly attributed to insulin resistance. Whether FGF21 contributes to the impaired bone quality in IGT remains speculative.

Lineage-specific differentiation of osteogenic progenitors from pluripotent stem cells reveals the FGF1-RUNX2 association in neural crest-derived osteoprogenitors.

Human pluripotent stem cells (hPSCs) can provide a platform to model bone organogenesis and disease. To reflect the developmental process of the human skeleton, hPSC differentiation methods should include osteogenic progenitors (OPs) arising from three distinct embryonic lineages: the paraxial mesoderm, lateral plate mesoderm, and neural crest. Although OP differentiation protocols have been developed, the lineage from which they are derived, as well as characterization of their genetic and molecular differences, has not been well reported. Therefore, to generate lineage‐specific OPs from human embryonic stem cells and human induced pluripotent stem cells, we employed stepwise differentiation of paraxial mesoderm‐like cells, lateral plate mesoderm‐like cells, and neural crest‐like cells toward their respective OP subpopulation. Successful differentiation, confirmed through gene expression and in vivo assays, permitted the identification of transcriptomic signatures of all three cell populations. We also report, for the first time, high FGF1 levels in neural crest‐derived OPs—a notable finding given the critical role of fibroblast growth factors (FGFs) in osteogenesis and mineral homeostasis. Our results indicate that FGF1 influences RUNX2 levels, with concomitant changes in ERK1/2 signaling. Overall, our study further validates hPSCs' power to model bone development and disease and reveals new, potentially important pathways influencing these processes.

P1823THE ROLE OF FGF-23 IN CKD PROGRESSION IN CHILDREN

Abstract Background and Aims Chronic kidney disease (CKD) is considered a global medical and public health issue. CKD takes a special place among non-infectious diseases because of its prevalence (6-20% according to different surveys and studies) and is associated with a poor life quality, complications and high risk of mortality. In recent years, there have been new biomarkers requiring more research in this area. One of these biomarkers is Fibroblast growth factor-23 (FGF-23) which is found as a bone derived hormone and might be a predictor of progression. However, the role of FGF-23 in CKD progression in children has not been adequately studied, especially on the early stages. Nowadays, the study of FGF-23 in children and the question of the clinical importance of this marker are relevant. Therefore, the aim of our study was to establish the role of FGF-23 in CKD progression in children. Method A prospective study was conducted on 73 children with different stages of CKD and 14 healthy individuals (control group) matched by age and gender. There were approximately equal numbers of patients in study groups. An average age was 9.61±1.05 years. Exclusion criteria: active inflammatory, bone, infectious, oncological, immunological diseases, taking steroids and vitamin D supplements. Laboratory measurements included all common clinical and biochemical indicators. Serum concentration of intact FGF-23 was assessed by using the ELISA method (Biomedica Medizinprodukte GmbH, Austria). Statistical analysis was conducted in MS Excel 2016 and SPSS 18.0. Results The normal range of FGF-23 for this kit was 0.1-1.5 pmol/l. The average value of FGF-23 in the control group was 0.69±0.12 pmol/l. Further studies in the groups with different stages of CKD revealed that FGF-23 concentration gradually rose in parallel with stages of CKD, and it reached the maximum on the last stage. It should be noticed that the level of FGF-23 concentration on the first stage of CKD was normal (0.73±0.14 pmol/l) and the comparison with healthy individuals revealed no significant differences. What is remarkable, despite the fact that the average value of the second stage patients was normal (1.36±0.2 pmol/l), there was a statistically significant difference with the control group (p=0.008). The levels of FGF-23 on the next stages were 2.52±0.52 pmol/l, 5.42±1.61 pmol/l, and 12.16±1.55 pmol/l, respectively. The differences were considerable and proved by statistical analysis (p&amp;lt;0.01). Conclusion Our study showed that there is an upward trend of FGF-23 as CKD progresses from early to advanced stages. The results on the second and third stages indicate that FGF-23 should be considered as one of early biomarkers of CKD progression in children. Thus, there is a need for more studies in this area.

FGF signaling is required for chemokinesis and ventral migration of trunk neural crest cells.

Neural crest cells (NCCs) delaminate from the neural tube (NT) and migrate ventrally to generate the trunk peripheral nervous system (PNS). Although several signaling pathways have been identified that steer NCCs once they are on their ventral trajectory, no molecules have been identified that are required for the initial migration between the NT and the dorsal root ganglion. Given the critical role of fibroblast growth factor (FGF) signaling in embryogenesis, we investigated its function in this initial migration. FGFR1 signaling is required for the migration of newly delaminated NCCs onto the ventral pathway. Live imaging of migrating NCCs revealed that inhibition of FGFR1 signaling caused the dorsally stalled NCCs to lose their dorsal/ventral oriented polarity and instead adopt a rounded morphology while dynamically extending filopodia. FGF8, an FGFR1 ligand, increased motility of NCCs away from the NT by acting chemokinetically. Finally, we provide evidence that inhibition of FGFR1-mediated chemokinesis is partially rescued by increasing Akt signaling, inhibiting RhoA, and activation of N-cadherin signaling. These data support a model in which NCCs are stimulated chemokinetically by FGF:FGFR1 signaling, and that this activation positions and orients NCCs on their ventral migratory route-a process that is essential for patterning the trunk PNS.

FGF23 and primary hyperparathyroidism: is there a link?

Data regarding the role of fibroblast growth factor 23 (FGF23) in primary hyperparathyroidism (PHPT) are scarce and discordant. Our study aimed to evaluate the prognostic impact of FGF23 upon the clinical and biochemical evolution of PHPT. Forty-two patients with ages between 30 and 80 years, diagnosed with PHPT caused by a sporadic, solitary parathyroid adenoma, and referred to surgery (minimally invasive parathyroidectomy) were prospectively included in the study. Serum levels of FGF23, PTH, 25(OH)D3, calcium (Ca), phosphate (P), total procollagen type 1 N-terminal propeptide, and C-terminal telopeptide of type I collagen were determined at baseline (preoperatory), one day after surgery, and in 13 patients also prospectively at three, six, and 12 months. Bone mineral density (BMD) was also evaluated before surgery in all patients and 12 months after surgery in the 13 followed up patients. In the 42 PHPT patients with D hypovitaminosis (mean 25(OH)D3 levels of 16.2 ± 1.5 ng/mL), preoperatory serum FGF23 concentration was within the normal range (75.55 ± 3.39 pg/mL) and remained unchanged one day post operation (81.69 ± 4.67 pg/mL, p = non-significant). The 13 patients followed prospectively for up to 12 months after surgery also showed unmodified FGF23 levels (80.9 ± 11.03 pg/mL, p = non-significant), despite PTH and Ca normalisation and vitamin D replenishment. Preoperatory FGF23 negatively correlated with PTH (r = -0.37, p = 0.038), but not with 25(OH)D3, Ca, P, bone mass, or metabolism markers. In PHPT, correlations between FGF23 and PTH seem rather an epiphenomenon. Therefore, we think that FGF23 evaluation and dynamics are not informative regarding PHPT severity. (Endokrynol Pol 2020; 71 (4): 306-312).

FGF signaling promotes myoblast proliferation through activation of wingless signaling

Indirect flight muscles (IFMs) are the largest muscles in Drosophila and are made up of hundreds of myonuclei. The generation of these giant muscles requires a large pool of wing disc associated adult muscle precursors (AMPs), however the factors that control proliferation to form this myoblast pool are incompletely known. Here, we examine the role of fibroblast growth factor (FGF) signaling in the proliferation of wing disc associated myoblasts. We find that the components of FGF signaling are expressed in myoblasts and surrounding epithelial cells of the wing disc. Next, we show that attenuation of FGF signaling results in a diminished myoblast pool. This reduction in the pool size is due to decreased myoblast proliferation. By contrast, activating the FGF signaling pathway increases the myoblast pool size and restores the proliferative capacity of FGF knockdown flies. Finally, our results demonstrate that the FGF receptor Heartless acts through up-regulating β-catenin/Armadillo signaling to promote myoblast proliferation. Our studies identify a novel role for FGF signaling during IFM formation and uncover the mechanism through which FGF coordinates with Wingless signaling to promote myoblast proliferation.

Evaluation of the Role of Fibroblast Growth Factors 23(FGF23) as a Marker for Left Ventricular Hypertrophy in Adults with Hypertension

Evaluation of the Role of Fibroblast Growth Factors 23(FGF23) as a Marker for Left Ventricular Hypertrophy in Adults with Hypertension

New Insights into the Role of FGF-23 and Klotho in Cardiovascular Disease in Chronic Kidney Disease Patients.

Alterations of fibroblast growth factor 23 (FGF-23) and Klotho levels are considered to be the earliest biochemical abnormality of chronic kidney disease - mineral and bone disease (CKDMBD) syndrome. Moreover, emerging data suggests that the dysregulated FGF-23 and Klotho axis has many effects on the cardiovascular (CV) system and contributes significantly to the increased CV morbidity and mortality rates of CKD patients. This review examines recent evidence on the role of FGF-23 and Klotho in the development and progression of CV complications of uremia namely cardiac hypertrophy, uremic cardiomyopathy, and atherosclerotic and arteriosclerotic vascular lesions. Moreover, the available evidence on their associations with adverse clinical outcomes are summarized. Undoubtedly, more studies are needed to further elucidate the effects of FGF-23 and Klotho on the heart and vessels and to gain insights into their prognostic value as CV risk factors. Finally, large prospective studies are required to test the hypothesis that modification of their levels would have a favourable impact on the unacceptably high mortality rates of these patient populations.

Role of fibroblast growth factor 4 in the growth and metastasis of colorectal cancer.

The role of fibroblast growth factor receptor4 (FGFR4) in colorectal cancer (CRC) is poorly characterized. Therefore, the objective of the current study was to investigate the expression levels of FGFR4 in colorectal cancer and its prognostic value, and clarify the role of FGFR4 in the proliferation and metastasis of colorectal cancer cells. Immunohistochemistry was used to detect the association between FGFR4 expression and clinicopathological features in colorectal cancer tissues. The effect of FGFR4 silencing on tumor cell proliferation, cell cycle, apoptosis, migration and invasion was evaluated via lentiviral transfection of the colorectal cancer cell line SW620. Western blot analysis was used to detect the changes of epithelial‑mesenchymal transition (EMT) markers, following FGFR4 silencing. FGFR4 is upregulated in CRC tissues compared with normal tissues. Patients with high FGFR4 expression exhibited a lower 5‑year survival rate compared with patients with low FGFR4 expression (64 vs.74%). FGFR4 silencing reduced proliferation, inhibited cell invasion, arrested cells in S phase and promoted apoptosis in colorectal cancer cells. FGFR4 silencing partially reversed EMT progression and FGFR4 this effect was enhanced in the presence of XAV939 (a β‑catenin inhibitor). The current data suggest that FGFR4 may be associated with prognosis in patients with colorectal cancer. Invitro functional tests revealed that FGFR4 may represent an effective therapeutic target for colorectal cancer. FGFR4 may also regulate EMT via the Wnt/β‑catenin pathway.

Initiation of Conceptus Elongation Coincides with an Endometrium Basic Fibroblast Growth Factor (FGF2) Protein Increase in Heifers.

Fibroblast growth factors (FGF) play an important role during embryo development. To date, the role of FGF and the respective receptors (FGFR) during the preimplantation phase in cattle are not fully characterized. We examined FGF1, FGF2, FGFR1, FGFR2, and FGFR3 in cyclic and early pregnant heifers at Days 12, 15, and 18 after insemination (Day 0). Endometrial FGF1 mRNA transcript abundance in heifers varied significantly with respect to the day after insemination, the pregnancy status, and their interaction. The expression was higher in nonpregnant than in pregnant heifers at Day 18. The conceptus transcripts abundance of FGFR2 and FGFR3 were significantly lower at Day 15 than 18. In the endometrium, FGF1 protein abundance significantly decreased from Day 12 onwards and FGF2 protein abundance showed a minor, but a significant increase at Day 15 in comparison to Days 12 and 18. We concluded that the decrease in FGF1 mRNA expression in pregnant heifers at Day 18 points towards a potential contribution of FGF1 in the preimplantation process. Additionally, successful embryo elongation might require a spatiotemporal FGF2 protein increase in the endometrium.

Progress in Research on the Role of FGF in the Formation and Treatment of Corneal Neovascularization.

Corneal neovascularization (CNV) is a sight-threatening disease usually associated with inflammatory, infectious, degenerative, and traumatic disorders of the ocular surface. Fibroblast growth factor (FGF) family members play an important role in angiogenesis to induce corneal neovascularization, which significantly affects the differentiation, proliferation, metastasis, and chemotaxis of vascular endothelial cells. Both acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) demonstrate positive staining in capillaries and induce corneal stromal cells. The anabolism of endothelial cells is induced by bFGF in corneal neovascularization. FGFs exert their effects via specific binding to cell surface-expressed specific receptors. We believe that both anti-FGF antibodies and anti-FGF receptor antibodies represent new directions for the treatment of CNV. Similar to anti-vascular endothelial growth factor antibodies, subconjunctival injection and eye drops can be considered effective forms of drug delivery.

Limited role for fibroblast growth factor 23 in assessing prognosis in heart failure patients: data from the TIME-CHF trial.

Fibroblast growth factor 23 (FGF23) is an intensively studied biomarker at the crossroads of cardiovascular disease, heart failure (HF) and chronic kidney disease. Independent associations between increasing FGF23 levels and cardiovascular events were found in many, but not all studies. By analysing data from the TIME-CHF cohort, we sought to investigate the prognostic value of FGF23 in an elderly, multimorbid HF patient cohort. We determined differences between intact (iFGF23) and C-terminal FGF23 (cFGF23) regarding their prognostic value and their levels over time in different HF subgroups according to left ventricular ejection fraction (LVEF). In this multicentre trial of 622 patients with symptomatic HF aged ≥60 years, we determined iFGF23 and cFGF23 at baseline, 3, 6 and 12-month follow-up. In unadjusted analyses, cFGF23 significantly predicted all HF-related outcomes at all time points. The predictive value of iFGF23 was less and not statistically significant at baseline. After multivariable adjustments, the association between both cFGF23 and iFGF23 and outcome lost statistical significance apart from cFGF23 at month 3. Overall, patients with preserved and mid-range LVEF had higher levels of iFGF23 and cFGF23 than those with reduced LVEF. Levels decreased significantly during the first 3months in mid-range and reduced LVEF patients, but did not significantly change over time in those with preserved LVEF. Fibroblast growth factor 23 is of limited value regarding risk prediction in this elderly HF population. Potentially heterogeneous roles of FGF23 in different LVEF groups deserve further investigation.

Fibroblast growth factor 10 alleviates particulate matter-induced lung injury by inhibiting the HMGB1-TLR4 pathway.

Exposure to particulate matter (PM) is associated with increased incidence of respiratory diseases. The present study aimed to investigate the roles of fibroblast growth factor 10 (FGF10) in PM-induced lung injury. Mice were intratracheally instilled with FGF10 or phosphate-buffered saline at one hour before instillation of PM for two consecutive days. In addition, the anti-inflammatory impact of FGF10 in vitro and its effect on the high-mobility group box 1 (HMGB1)-toll-like receptor 4 (TLR4) pathway was investigated. It was found that PM exposure is associated with increased inflammatory cell infiltration into the lung and increased vascular protein leakage, while FGF10 pretreatment attenuated both of these effects. FGF10 also decreased the PM-induced expression of interleukin (IL)-6, IL-8, tumor necrosis factor-α and HMGB1 in murine bronchoalveolar lavage fluid and in the supernatants of human bronchial epithelial cells exposed to PM. FGF10 exerted anti-inflammatory and cytoprotective effects by inhibiting the HMGB1-TLR4 pathway. These results indicate that FGF10 may have therapeutic values for PM-induced lung injury.

Studies on tail regeneration and homeotic transformation in anuran tadpoles.

Anuran tadpoles are excellent models for regeneration studies. The tail, an organ essential for swimming for the aquatic tadpole, regenerates completely following injury or amputation. However, treatment with the morphogen, vitamin A or retinoic acid inhibits normal tail regeneration and induces homeotic transformation of tail to limbs. This phenomenon was discovered for the first time in the Indian marbled balloon frog Uperodon systoma in the Developmental Biology laboratory of Utkal University (Odisha, India) in the year 1992. In this paper, we present the results of morphological, histological, biochemical and molecular (immonohistochemistry) investigations of vitamin A induced homeotic transformation in different anuran species. In addition, we discuss the putative role of fibroblast growth factor 1 during spinal cord regeneration in the tadpoles of the Indian tree frog, Polypedates maculatus, an ideal model for regeneration studies in an Indian context.

FGF/FGFR signaling pathway involved resistance in various cancer types

Resistance becomes major clinical issue in cancer treatment, which strongly limits patients to benefit from oncotherapy. Growing evidences have been indicative of the critical role of fibroblast growth factor (FGF)/receptor (FGFR) signaling played in resistance to oncotherapy. In this review we discussed the underlying mechanisms of FGF/FGFR signaling mediated resistance to chemotherapy, radiotherapy and target therapy in various cancers. Meanwhile, we summarized the reported mechanism of FGF/FGFR inhibitors resistance in cancers.

Ethanol induced increase of fibroblast growth factor 2 mRNA content in emotiogenic brain structures of rats

We studied the effects of acute, subacute, and chronic alcohol treatment of rats on the content of fibroblast growth factor 2 (FGF2) mRNA in various brain structures. Results suggest a possible role of FGF2 in the functioning of dopaminergic neurons in the midbrain. In our experiment, ethanol treatment of rats was accompanied by an increase in the FGF2 mRNA level in the emotiogenic structures of the brain. This effect was blocked by pretreatment of animals with chlorpromazine. This suggests FGF2 involvement in the mechanisms of alcohol dependence and can be considered as a possible diagnostic and therapeutic target in alcoholism.

Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD): Current Perspectives.

Despite the availability of global and regional guidelines to curtail the adverse clinical outcomes associated with chronic kidney disease–mineral and bone disorder (CKD-MBD), most CKD patients are still affected by the consequences of abnormalities of CKD-MBD. This important clinical complication of CKD continues to be studied, in order to improve the understanding and management of CKD-MBD. Some notable discoveries include the role of fibroblast growth factor 23 (FGF23) in the pathogenesis of CKD-MBD, leading to a shift from the previous well-established classic trade-off hypothesis to the updated trade-off hypothesis. More recently, there has been a shift from the treatment of CKD-MBD based on a single level of biomarkers to serial measurements of calcium, phosphate and parathyroid hormone (PTH). Furthermore, some clinical trials have emerged after the 2009 Kidney Disease-Improving Global Outcomes (KDIGO) Guidelines, leading to the 2017 KDIGO updated recommendations. Hence, this review gives an overview of the rapidly evolving trends in CKD-MBD, linking the past and current concepts of CKD-MBD.

Expression and functional role of fibroblast growth factors (FGF) in placenta during different stages of pregnancy in water buffalo (Bubalus bubalis)

The present study documented the expression and functional role of Fibroblast growth factors (FGFs) family and their receptors (Fibroblast growth factor receptor, FGFRs) in placenta (Cotyledon; COT, Caruncle; CAR) during different stages of pregnancy in water buffalo. Samples were collected from Early pregnancy 1 (EP1); Early pregnancy 2 (EP2); Mid pregnancy (MP) and Late pregnancy (LP) while diestrus stage of oestrus cycle (NP) was taken as control. In addition, modulatory role of FGF2 on mRNA expression of von Willebrand factor (vWF), Proliferating cell nuclear antigen (PCNA), steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage (CYP11A1), 3β-hydroxysteroid dehydrogenase (3βHSD) and BCL2 Associated X (BAX) were studied in cultured trophoblast cells (TCC), obtained from EP2. Real-time PCR (qPCR), Western blot, and immunohistochemistry were applied to investigate mRNA and protein expressions, and the localization of examined factors whereas, P4 secretion was assessed by RIA. The mRNA and protein expression of FGFs and its receptors were maximum (P < 0.05) during EP (EP1 and EP2) in COT. However, FGFR1 and FGFR4 were upregulated (P < 0.05) during EP2 and MP in COT. Similarly, the mRNA and protein expression of FGFs and its receptors were upregulated (P < 0.05) during all stages of pregnancy in CAR. FGF family members were localized in the cytoplasm of trophoblast cells as well as in fetal blood vessels. At 100 ng/ml dosage, FGF2 stimulated the transcript of vWF maximally (P < 0.05). P4 secretion in trophoblast cells treated with FGF2 was maximum with the highest dose at 72 h. These findings corroborate that FGF acts locally in the trophoblast cells to modulate steroid hormone viz. progesterone synthesis, promote angiogenesis and favors cell survivability indicating that this factor may play an essential role in the regulation of placental formation and function in buffalo.